A patient living with HIV who received a blood stem cell transplant for high-risk acute myeloid leukemia has been free of the virus for 14 months after stopping HIV antiretroviral drug treatment, suggesting a cure, according to the Weill Cornell Medicine physician-scientists who performed the transplant and managed her care. As in two other successful cases that have been reported, the transplanted donor cells bore a mutation that makes them resistant to HIV infection.

The new case of long-term HIV remission was reported on Feb. 15 at the 29th annual Conference on Retroviruses and Opportunistic Infections, in Denver.

The patient received transplants of blood- and immune-cell replenishing stem cells after having her own blood cell population, including leukemic cells, destroyed by high-dose chemotherapy. The transplanted cells came from two sources: stem cells from a healthy adult relative were used to quickly restore her blood cell population to reduce infectious complications, and umbilical cord blood from an unrelated newborn child was used to provide long-term blood reconstitution.

Cord blood is used to supply blood stem cells for transplants for patients unable to find matched adult donors. Transplant specialists have found that cord blood may be used successfully even when they come from an unrelated donor whose immune markers only partially match the recipients.

Doctors in this case used cord blood containing an HIV-resistance gene variant called CCR532. HIV normally uses the CCR5 co-receptor to help it infect immune cells, but the receptors 32 variant effectively blocks viral entry.

Three months after the transplant, tests showed that the patients blood cell population was entirely derived from the HIV-resistant cord blood cells. Post-transplant studies could no longer detect HIV by various sensitive assays. The patient eventually stopped taking antiretroviral drugs to suppress her HIV infection, and so far, has been off the HIV drugs for 14 months, with no signs of HIV re-emergence after close follow-up during COVID 19 pandemicindicating a likely cure, although physicians at this stage prefer to call it long-term remission. She has also been leukemia-free for more than four years.

Two prior cases of long-term remission in HIV-positive cancer patients after adult CCR532 stem cell transplantation have been reported. This case is the first to use cord blood cells, and the first to treat a woman and someone who identifies as mixed-race. Since the CCR532 variant is much more common in people of European heritage, it is harder to find well-matched CCR532 donors for traditional stem cell transplants into nonwhite patients, although the use of cord blood partly alleviates this problem.

Stem cell transplant specialists Dr. Jingmei Hsu and Dr. Koen Van Besien and infectious disease specialist Dr. Marshall Glesby were the physician-scientists who led the NIH-funded clinical trial at Weill Cornell Medicine in collaboration with investigators at University of California Los Angeles, Johns Hopkins University School of Medicine and several other institutions.

The investigators concluded that cord blood containing the CCR532 variant offers a possible cure for both hematological malignancies and HIV and should be considered as a stem cell source when HIV-positive cancer patients need blood stem cell transplants. However, the procedure is considered too risky for HIV-positive patients who otherwise dont need such transplants.

Many Weill Cornell Medicine physicians and scientists maintain relationships and collaborations with external organizations to foster scientific innovation and provide expert guidance. Weill Cornell Medicine and its faculty make this information available to the public to ensure transparency. External relationship information is available on the faculty profiles of Dr. Jingmei Hsu, Dr. Koen Van Besien, and Dr. Marshall Glesby.

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Patient Possibly Cured of HIV Infection by Special Stem ...

Researchers led by Yevgeny Brudno, PhD, in the UNC-NCSU Joint Biomedical Engineering Department, have developed an implantable biotechnology that produces and releases CAR-T cells for attacking cancerous tumors.

Researchers from North Carolina State University and the University of North Carolina at Chapel Hill have developed an implantable biotechnology that produces and releases CAR-T cells for attacking cancerous tumors. In a proof-of-concept study involving lymphoma in mice, the researchers found that treatment with the implants was faster and more effective than conventional CAR-T cell cancer treatment.

T cells are part of the immune system, tasked with identifying and destroying cells in the body that have become infected with an invading pathogen. CAR-T cells are T cells that have been engineered to identify cancer cells and destroy them. CAR-T cells are already in clinical use for treating lymphomas, and there are many clinical trials under way focused on using CAR-T cell treatments against other forms of cancer.

A major drawback to CAR-T cell treatment is that it is tremendously expensive hundreds of thousands of dollars per dose, says Yevgeny Brudno, corresponding author of the study and assistant professor in the joint biomedical engineering department at NC State and UNC.

Due to its cost, many people are shut out from this treatment. One reason for the high cost is that the manufacturing process is complex, time-consuming and has to be tailored to each cancer patient individually, Brudno says. We wanted to address challenges in CAR-T treatment related to both manufacturing time and cost.

Reducing the manufacturing time is even more critical for patients with rapidly progressing disease, says Pritha Agarwalla, lead author of the study and a postdoctoral researcher in the joint biomedical engineering department.

To tackle this challenge, the researchers created a biotechnology called Multifunctional Alginate Scaffolds for T cell Engineering and Release (MASTER). The work was done in partnership with Gianpietro Dotti, professor in the Department of Microbiology and Immunology and co-leader of the Immunology Program at the Lineberger Cancer Center at UNC; and Frances Ligler, formerly the Ross Lampe Distinguished Professor of Biomedical Engineering at NC State and UNC and currently professor and Eppright Chair in Biomedical Engineering at Texas A&M.

To understand how MASTER works, you have to understand how CAR-T cells are produced. Clinicians first isolate T cells from patients and transport them to a clean manufacturing facility. At this facility, researchers activate T cells with antibodies over several days, preparing them for reprogramming. Once T cells are activated, researchers use viruses to introduce the CAR gene, reprogramming the T cells into CAR-T cells that target cancer cells. Researchers then add factors to stimulate the CAR-T cells to proliferate, expanding their number. Finally, after these manipulations are complete a process that can take weeks the cells are brought back to the hospital and infused into the patients bloodstream.

Our MASTER technology takes the cumbersome and time-consuming activation, reprogramming and expansion steps and performs them inside the patient, Agarwalla says. This transforms the multi-week process into a single-day procedure.

MASTER is a biocompatible, sponge-like material with the look and feel of a mini marshmallow. To begin treatment, researchers isolate T cells from the patient and mix these nave (or non-activated) T cells with the engineered virus. Researchers pour this mixture on top of the MASTER, which absorbs it. MASTER is decorated with the antibodies that activate the T cells, so the cell activation process begins almost immediately. Meanwhile, MASTER is surgically implanted into the patient in these studies, a mouse.

After implantation, the cellular activation process continues. As the T cells become activated, they begin responding to the modified viruses, which reprogram them into CAR-T cells.

The large pores and sponge-like nature of the MASTER material brings the virus and cells close together, which facilitates cellular genetic reprogramming, says Agarwalla.

The MASTER material is also impregnated with factors called interleukins that foster cell proliferation. After implantation, these interleukins begin to leach out, promoting rapid proliferation of the CAR-T cells.

Engineering the material so that it is dry and absorbs this combination of T cells and virus is critically important, Brudno says. If you try to do this by applying T cells and virus to a wet MASTER, it just doesnt work.

In these studies, the researchers worked with mice that had lymphoma. One group was treated with CAR-T cells that were created and delivered using MASTER. A second group was treated with CAR-T cells that were created conventionally and delivered intravenously. These two groups were compared to control group receiving non-engineered T cells.

Our technology performed very well, Brudno says. It would take at least two weeks to create CAR-T cells from nave T cells for clinical use. We were able to introduce the MASTER into a mouse within hours of isolating nave T cells.

In addition, since cells are implanted within hours of isolation, the minimal manipulation creates healthier cells that exhibit fewer markers associated with poor anti-cancer performance in CAR-T cells. Specifically, the MASTER technique results in cells that are less differentiated, which translates to better sustainability in the body and more anti-cancer potency. In addition, the cells display fewer markers of T-cell exhaustion, which is defined by poor T cell function.

The end result is that the mice that received CAR-T cell treatment via MASTER were far better at fighting off tumors than mice that received conventional CAR-T cell treatment, Agarwalla says.

The improvement in anti-cancer efficacy was especially pronounced over the long term, when mice were faced with a recurrence of lymphoma.

The MASTER technology was very promising in liquid tumors, such as lymphomas, but we are especially eager to see how MASTER performs against solid tumors including pancreatic cancer and brain tumors, Brudno says.

Were working with an industry partner to commercialize the technology, but theres still a lot of work to be done before it becomes clinically available. Further work to establish the safety and robustness of this technology in animal models will be necessary before we can begin exploring clinical trials involving human patients.

While its impossible to estimate what the cost of MASTER treatment might be if it is eventually approved for clinical use, Brudno says hes optimistic that it would be substantially less expensive than existing CAR-T treatment options.

Were also exploring opportunities with other industry partners for taking the fundamental concepts of MASTER and applying them for use in regenerative medicine and in treating autoimmune disease, Brudno says.

I feel like were just scratching the surface of whats possible here, Agarwalla says.

The paper, Bioinstructive Implantable Scaffolds for Rapid In Vivo Manufacture and Release of CAR-T Cells, is published in Nature Biotechnology. The paper was co-authored by Kristen Froehlich, a former undergraduate at NC State; Edikan Ogunnaike, Sarah Ahn of UNC; and Anton Jansson of NC State.

The work was done with support from the North Carolina Biotechnology Center, under flash grant 2019-FLG-3812; from the National Center for Advancing Translational Sciences; and from the National Institutes of Health under grants UL1TR002489, R01CA193140, R21-CA229938-01A1, T32CA196589 and R25NS094093.

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INDIANAPOLIS, March 24, 2022 /PRNewswire/ -- Eli Lilly and Company (NYSE: LLY) today announced that the U.S. Food and Drug Administration (FDA) has issued a complete response letter (CRL) for the Biologics License Application (BLA) for the investigational medicine sintilimab injection, a PD-1 inhibitor in combination with pemetrexed and platinum chemotherapy for the first-line treatment of people with nonsquamous non-small cell lung cancer (NSCLC). Sintilimab is being developed by Innovent Biologics, Inc. (HKEX: 01801) and Lilly.

The letter indicates that the review cycle is complete but the FDA is unable to approve the application in its current form, consistent with the outcome of the Oncologic Drugs Advisory Committee Meeting in February. The CRL includes a recommendation for an additional clinical study, specifically a multiregional clinical trial comparing standard of care therapy for first line metastatic NSCLC to sintilimab with chemotherapy utilizing a non-inferiority design with an overall survival endpoint.

Along with Innovent, Lilly is assessing next steps for the sintilimab program in the U.S.

About SintilimabSintilimab, is an investigational PD-1 inhibitor developed by Innovent and Lilly. Sintilimab is a type of immunoglobulin G4 monoclonal antibody, which binds to PD-1 molecules on the surface of T-cells, blocks the PD-1 / PD-Ligand 1 (PD-L1) pathway, and reactivates T-cells to kill cancer cells. Innovent is currently conducting more than 20 clinical studies of sintilimab to evaluate its safety and efficacy in a wide variety of cancer indications, including more than 10 registrational or pivotal clinical trials.

In China, sintilimab, marketed as TYVYT (sintilimab injection), has been approved for:

Additionally, Innovent currently has regulatory submissions under review in China for sintilimab:

Sintilimab was included in China's National Reimbursement Drug List (NRDL) for all four approved indications (listed above), according to the latest announcement from the China National Healthcare Security Administration ("NHSA").

About Eli Lilly and CompanyLilly is a global healthcare leader that unites caring with discovery to create medicines to make life better for people around the world. We were founded more than a century ago by a man committed to creating high-quality medicines that meet real needs, and today we remain true to that mission in all our work. Across the globe, Lilly employees work to discover and bring life-changing medicines to those who need them, improve the understanding and management of disease, and give back to communities through philanthropy and volunteerism. To learn more about Lilly, please visit http://www.lilly.com/and lilly.com/newsroom.

Lilly USA, LLC 2022. ALL RIGHTS RESERVED.

About Innovent Biologics' Strategic Collaboration with Eli Lilly and CompanyInnovent entered into a strategic collaboration with Lilly focused on biological medicine in March 2015 a groundbreaking partnership between a Chinese pharmaceutical company and a multinational pharmaceutical company. Under the agreement, Innovent and Lilly are co-developing and commercializing oncology medicines, including sintilimab in China. In October 2015, the two companies announced the extension of their existing collaboration to include co-development of three additional oncology antibodies targeting oncology indications. In August 2019, Innovent further entered a licensing agreement with Lilly to develop and commercialize a potentially global best-in-class diabetes medicine in China. Its collaboration with Lilly indicates that Innovent has established a comprehensive level of cooperation between China's innovative pharmaceuticals sector and the international pharmaceuticals sector in fields such as R&D, CMC, clinical development and commercialization. In August 2020Lilly and Innovent announced a global expansion of their strategic alliance for sintilimab, whereby Lilly obtained an exclusive license for sintilimab for geographies outside of China.

Note:TYVYT (sintilimab injection; Innovent) and BYVASDA (bevacizumab biosimilar injection; Innovent) are not approved products in the United States.

Eli Lilly and Company Forward-Looking StatementThis press release contains forward-looking statements (as that term is defined in the Private Securities Litigation Reform Act of 1995) about sintilimab injection in combination with pemetrexed and platinum chemotherapy as a potential first-line treatment of people with nonsquamous non-small cell lung cancer and reflects Lilly's current beliefs and expectations. However, as with any pharmaceutical product, there are substantial risks and uncertainties in the process of drug research, development, and commercialization. Among other things, there can be no guarantee that future study results will be consistent with study results to date, or that sintilimab will receive additional regulatory approvals or be commercially successful. For further discussion of these and other risks and uncertainties, see Lilly's most recent Form 10-K and Form 10-Q filings with the United States Securities and Exchange Commission. Except as required by law, Lilly undertakes no duty to update forward-looking statements to reflect events after the date of this release.

Refer to:

Lauren Cohen; lcohen@loxooncology.com; (617) 678-2067 (media)

Kevin Hern; hern_kevin_r@lilly.com; (317) 277-1838 (investors)

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Bluebird bio has spent the better part of two decades developing gene therapies for rare diseases. This summer, after years of clinical trials, setbacks and delays, two of its experimental treatments could secure approval in the U.S.

Yet Bluebird is in a precarious position. The company warned investors this month that, with cash reserves dwindling rapidly, there is "substantial doubt" about its ability to remain solvent for the coming year.

Bluebird isn't the only cell and gene therapy developer facing a financial bind. Since December, at least nine other biotech companies working in the field have announced layoffs, cost cuts or restructured their research. Two others have sold off their manufacturing operations.

The retrenchment coincides with the sharpest market downturn for publicly traded drugmakers in years, which has forced tough choices on young startups and more established biotechs alike.

"We're seeing valuations for companies take a hit, down to the point that we're seeing multiple companies at negative enterprise value, which really is quite shocking to see," said Nessan Bermingham, a venture capitalist and former CEO of the gene editing biotech Intellia Therapeutics.

The stock market pain is shared by companies in other sectors of the biotech industry beyond cell and gene therapy, but developers of those types of medicines appear vulnerable.

Many aren't yet in the clinic and have yearslong research journeys ahead of them before it's clear whether their experimental treatments are likely to work. Developing and manufacturing gene therapies is also an expensive endeavor, stressing balance sheets at a moment when new investment is harder to come by.

Moreover, a string of clinical and regulatory stumbles has sapped investors' confidence in the ability of gene therapy companies to reliably turn cutting-edge science into approvable medicines.

"It's not a perfect storm, but it's a confluence of a lot of elements driving the issues we're seeing," said Bermingham, now an operating partner with Khosla Ventures.

For Amicus Therapeutics, a small biotech that for the past three years has built a pipeline of gene therapies, the market downturn hit at an inopportune time.

Last September, in somewhat better times for biotech stocks, Amicus announced plans to spin out its gene therapy business via a merger with a blank-check company. But by February, it was forced to call off the deal, citing "unfavorable market conditions" and an "increasingly challenging environment for stand-alone gene therapy companies."

As a result, Amicus said it would no longer advance multiple gene therapies into the clinic as intended and suspended plans to build a manufacturing plant. Thirty-five employees, or about 7% of the company, were laid off, most of whom had been involved in R&D.

Since December, Sigilon Therapeutics, Freeline Therapeutics, Gemini Therapeutics and Passage Bio have been forced to cut jobs as well. Meanwhile, Generation Bio, Avrobio, Sio Gene Therapies and Graphite Bio have reset their research, prioritizing certain experimental drugs or areas of research while stepping back from others.

"When you are in a position where you have to conserve capital, you are often going to prioritize indications where you believe have a higher probability of success as well as less competitive dynamics," said Luca Issi, an analyst at RBC Capital Markets. "We're going to see more of that."

The gene therapy contraction contrasts sharply with the past several years, during which new gene therapy companies won substantial funding and outlined expansive drug development plans. Since 2018, nearly 50 biotechs working on either cell or gene therapies priced an initial public offering. About half had yet to enter clinical testing at the time of their IPO Generation and Graphite among them.

While they weren't alone dozens of other biotechs outside of gene therapy did the same during the same period those companies are now more exposed as investors adjust their expectations for gene therapy.

"We saw a lot of companies go very early on," said Bermingham. "That's OK when markets are really strong," he added, but "becomes more challenging" in a downturn.

To Gbola Amusa, chief scientific officer at Chardan, the flood of preclinical companies launching IPOs in recent years has meant the average gene therapy biotech is less mature and therefore more susceptible to changing market conditions.

"A lot of the missteps and things we're hearing, sometimes it's because of [scientific challenges]," Amusa said. "The other times it's because of small companies that went public maybe too soon and are basically publicly traded academic enterprises without the capabilities that we would see with bigger biotechs."

As gene therapy companies have proliferated, so too has the number of experimental treatments entering clinical testing. According to the latest count by the Alliance for Regenerative Medicine, an industry group, there are more than 200 trials of gene therapies underway, with hundreds more in cell therapy.

One consequence of that progress is that more companies are running into problems in testing, whether due to newly uncovered safety risks or because of lower-than-expected efficacy.

Last year, Bluebird, UniQure and Allogene Therapeutics each halted studies after clinical trial participants developed cancer or, in the case of Allogene, signs of unusual DNA abnormalities. While all three companies were able to exonerate their treatments, the reports resurfaced concerns of whether gene therapy could heighten the risk of cancer.

The Food and Drug Administration has also appeared to be proceeding cautiously, even as it expects to approve more and more cell and gene therapies in the coming years. Last September, the agency convened a panel of experts to discuss one common type of gene therapy, a meeting that Bermingham said raised "orange flags" for companies in the field.

The FDA also issued more clinical holds, or regulatory suspensions, for cell and gene therapy trials in 2021 than in previous years. According to a Feb. 27 note from analysts at Jefferies, cell and gene therapy holds accounted for approximately 40% of those ordered by the regulator last year, despite representing well below that proportion of trials.

Beyond setting back individual companies, the trial halts might also be sparking broader questions about regulatory requirements and whether the field needs to do more work preclinically to assess certain risks.

On the other hand, clinical trial successes from more advanced cell and gene therapy developers could force companies earlier in testing to redraw their plans, particularly as many target some of the same rare diseases.

"I think you're going to see some of the business models and strategies be put under pressure by data that's come out from various groups," said Bermingham.

While more cell and gene therapy companies might restructure as stock prices remain depressed, clinical and regulatory progress from others could restore some of the field's attraction.

Beyond Bluebird's two treatments now up for approval, UniQure and BioMarin Pharmaceutical are expected to soon file for approval of gene therapies for hemophilia B and A, respectively. A sickle cell treatment from CRISPR Therapeutics and Vertex Pharmaceuticals is also nearing an FDA review.

Most large pharmaceutical companies are now invested in cell and gene therapy, too, buoying the partnership and acquisition activity that investors seek when backing new startups.

"Innovation takes time," said RBC's Issi. "We live in a bear market and gene therapy companies, many of them have limited cash. They are thinking creatively of how to continue to innovate."

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As biotech retreats, gene therapy companies retrench and redraw plans - BioPharma Dive

With obesity levels in the United States on the rise, researchers are studying what contributes to this condition at a molecular level.

Researchers from Ireland and Germany believe they have isolated specific cells that contribute to the inflammation associated with obesity. Their study, which appears in the journal Science Translational Medicine, addresses how managing certain cell components can help reduce obesity and the risk of related diseases such as type 2 diabetes.

According to 20172018 data from the Centers for Disease Control and Prevention (CDC), obesity affected 42.4% of adults in the U.S.

Health experts consider people overweight when their body mass index (BMI) reaches 25 and obese with a BMI of 30.

Several factors contribute to obesity, including food consumption and activity levels, but researchers are increasingly calling into question the so-called energy balance hypothesis of obesity. Trauma, stress, and some medications, such as steroids, can also contribute to weight gain.

Inflammation is a contributing factor to obesity. There are two types of inflammation: acute and chronic.

Acute inflammation occurs during an injury or infection. The immune system releases cytokines that aid in healing.

However, chronic inflammation is long lasting and can occur when a persons immune system is constantly overstimulated. When this occurs, certain functions in the body become dysregulated.

One major health issue relating to chronic inflammation is obesity.

Adipose tissue, or body fat, produces a type of cytokines. Health experts think an excessive amount of these proteins in people with obesity dysregulates the body, which could lead to metabolic disorders and heart disease.

Fat has traditionally been thought of as a passive storage organ for excess energy, but over the past couple of decades, it has been increasingly understood to have a huge number of other roles involved in metabolic signaling, Dr. Victoria Salem said in an interview with Medical News Today.

It has a rich blood and nerve supply and a complex interaction with the hormonal and immune systems.

Dr. Salem is a fellow in the Department of Bioengineering and an honorary consultant in Diabetes, Endocrinology, and General Internal Medicine at Victoria at Imperial College London.

The researchers speculated that the molecule PD-L1 plays a role in developing obesity. PD-L1 is a checkpoint protein involved in cell signaling within the immune system.

According to the authors, PD-L1 regulates adipose tissue immune cell composition.

Increasing evidence demonstrates profound dysregulation of the immune system in people with obesity [] leading to a state of low-grade inflammation, the authors write.

With this in mind, the researchers compared wild-type mice and mice genetically altered to lack PD-L1 in different types of cells, including dendritic, T cells, macrophages, and innate lymphoid cells. They fed both groups of mice a high fat diet and then compared which group had more weight gain.

They found that the mice lacking PD-L1 on their dendritic cells gained significantly more weight after 12 weeks on the high fat diet. This group also had increased insulin resistance, which leads to type 2 diabetes.

According to the authors, These results clearly demonstrate a critical role of the immunoregulator PD-L1 for the control of obesity.

This new process of checkpoint regulation of cells in visceral fat of obese individuals advances our understanding of how the immune system controls diet-induced weight gain that can lead to conditions such as obesity and type 2 diabetes, says study co-lead author Professor Padraic Fallon.

Prof. Fallon is the head of the Translational Immunology Group from Trinity College Dublins School of Medicine in Ireland.

After establishing the importance of PD-L1 in obesity with mice, the scientists accessed human studies and found that PD-L1 was up-regulated in people with obesity.

Only through our basic research efforts using preclinical models were we able to gain access to patients samples and link our findings to human disease, says co-lead author Dr. Christian Schwartz.

Dr. Schwartz is a principal investigator at University Hospital Erlangen in Germany.

The researchers hope that learning the importance of PD-L1 will factor into future weight loss treatments.

It will be interesting to investigate now how we can manipulate this checkpoint on specific cell populations of interest to help people with obesity, says Dr. Schwartz.

Dr. Mir Ali, a bariatric surgeon, spoke with MNT on the study findings.

This article is interesting in that another physiological pathway to obesity seems to be clarified, commented Dr. Ali. Since obesity is a complex interaction of hormonal and metabolic interactions, this sheds light on another mechanism.

In addition to being a surgeon, Dr. Ali is also medical director of MemorialCare Surgical Weight Loss Center at Orange Coast Medical Center in Fountain Valley, California.

Dr. Ali thinks the surgery could give hope to people with obesity in the future.

Potentially, there is a possibility of finding a safe and effective medication that may block this pathway to obesity, Dr. Ali said.

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Obesity and immune cells: What's the link? - Medical News Today

A medical consultation that turned into an idea exchange chat and led to the launch of a company that, in a nutshell, is how Eyestem came into existence.

This cell therapy company was founded by a group of doctors and management consultants whose vision was to create a cell therapy platform to treat incurable diseases and make these technologies accessible to everyone.

Talking about its inception, co-founder and Chief Executive Officer Jogin Desai says, I met Rajani Battu, a senior ophthalmologist, in 2014 for a medical consultation. Both of us saw cell and gene therapy as the next frontier of medical innovation and the eye being the prime target for these therapies. We discussed that the approach taken by the western companies will result in therapies that will cost more than $400,000 per injection. We felt this was the right time to disrupt the field.

Cell and gene therapy is going to lead to a paradigm shift in healthcare. Diseases that were deemed incurable will start getting treatment because of this, say experts. Indian patients can benefit if a base is created here for these new platforms. Currently, such treatments are not sustainable due to the astronomical costs a therapy for spinal muscular atrophy can cost Rs 16 crore per patient. Eyestem intends to change that by keeping the cost low.

Big challengesEyestem treats incurable diseases by replacing the cells that are lost to conditions such as idiopathic pulmonary fibrosis, age-related macular degeneration and retinitis pigmentosa.

Age-related macular degeneration (AMD) is a leading cause of incurable blindness in the industrialised world. About 170 million people suffer from this disease; 40 million in India. It presents as two variants: wet and dry. Wet AMD is treatable and the global market value for this is about $8 billion.

Dry AMDs incidence is 9 times that of wet AMD and is incurable. Eyestems lab grown suspension of RPE cells helps in treating this condition. Retinitis pigmentosa (RP) is a group of rare, genetic disorders that affects children and causes complete vision loss by the age of 20. Some 5 million kids are estimated to suffer from this disease; 1.5 million in India. Eyecytes lab grown suspension of photoreceptor progenitor cells can be used to rescue the vision of these children. Idiopathic pulmonary fibrosis (IPF) is a serious chronic disease that makes breathing difficult and leads to cardiovascular complications. Once diagnosed, patients have a median survival period of 3-5 years. It is estimated that 5-6 million suffer from this globally. The companys lab grown suspension of cells can lead to improvement of the condition.

The company treats incurable diseases by replacing the cells that are lost to conditions such as idiopathic pulmonary fibrosis. (Pic: Team Eyestem)

A question of affordabilityThe company claims to be capital efficient and aims to get each product from concept to human trials in under $4 million. Most pharma companies spend 10 times this number to reach this stage, claims Desai.

On how soon the treatments can be commercialised, he says, Our treatment of dry AMD will go through first human trials by Q4 2022 and each new product to treat incurable diseases will be deployed 12 months after that. All of these are unmet needs and hence go through a fast-track clinical trial process. We expect to begin commercial availability of our flagship product by the end of 2024.

One of the experts in stem cells and regenerative medicine who is on the advisory board of the startup is Mahendra Rao, former Director of NIH Center for Regenerative Medicine (Washington, DC) and the CEO of Implant Therapeutics. He says he was impressed with the co-founders approach to work. They have ensured early engagement with DGCI and the FDA for their input and added experts to the board to ensure that their work meets international standards. They coordinated with LV Prasad Eye Hospital to help design a trial that is best suited for Indian patients."

Matter of fundingThe company says that it has been selective in raising funds as its purpose is not to raise money with higher valuations but to help patients. With its latest round of funding, it aims to upgrade its manufacturing process and deploy artificial intelligence to increase the predictability of its protocols. The company underscores they prefer to not talk about the money raised or valuation as their focus is not on such irrelevant metrics.

The angel round was led by myself and my team of senior ex-Quintiles executives from India, South Africa and Zurich. Endiya Partners and Kotak Private Equity joined in a subsequent pre-series A round. We are currently raising our series A and we are halfway there. 30% has been committed by current shareholders and we have soft commitment from a global venture fund for the other 20%. We anticipate closing this round in the next 8-12 weeks, adds Desai.

Nitin Deshmukh, senior advisor at Kotak Investment Advisors, says, Eyestem has taken a leadership position in developing allogeneic cell therapy products for ophthalmic conditions. We are happy with initial results seen in the product for treatment of age-related macular degeneration (AMD), a retinal degenerative disease.

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Disclaimer: Please note that all opinions from this article are from the participants perspectives. Every patient experience is unique, so its important to talk with your doctor about what is best for you.

In a matter of minutes, a small cell lung cancer (SCLC) diagnosis can quickly flip your world upside down. You may feel overwhelmed, or even guilty, but it can be reassuring to know you are not alone in this. Approximately 30,00035,000 people are diagnosed with SCLC each year in the United States.

Oncology Nurse Practitioner Cindy Cherry, MSN, AGNP-C, has years of experience helping people through their diagnosis, physically and emotionally. She often shares advice to keep her patients motivated during this tumultuous time. My number one goal is to help make sure my patients understand that no one deserves cancer, and it is something you and your care team will fight together. Concentrate on moving forward, said Cherry.

Chemotherapy treatment usually begins shortly after a diagnosis is received. Your care team will determine what treatment approach is best based on your needs. At this point, Cherry encourages her patients to begin treatment with a flexible, open mind. Try to not already have it set in your mind how you think this is going to go so that you can fully explore all the options your doctor recommends, she said.

While you may want to compare your treatment to others, side effects can vary from person to person depending on diagnosis and certain chemotherapies. Treatment looks different for everyone, so try to only focus on what youre going through.

Even second or third cancer survivors can receive completely different treatment for each diagnosis. SCLC patient Dorothy T. from North Carolina has received three separate lung cancer diagnoses with very different treatment experiences.

Dorothys first diagnosis in 2014 was non-small cell lung cancer, and instead of receiving chemotherapy, a portion of her lung was removed, which meant she had to continuously undergo checkups for the next 5 years. Then in 2019, Dorothys oncologist discovered an unfortunate sight: her cancer was back, and it was SCLC. This second diagnosis was a little different; she was going to receive chemotherapy.

This first experience with chemotherapy was grim and she swore shed never endure it again. I really thought I was dying, said Dorothy. I was so weak and tired that Id fall on the floor at night going to the bathroom. I couldnt take a shower for five days.

The extreme fatigue Dorothy experienced during her first chemotherapy treatment can sometimes be a sign of bone marrow suppression, which can happen when a patient receives chemotherapy. Bone marrow suppressionalso known as myelosuppressionis a serious side effect of chemotherapy treatment that occurs when chemotherapy damages blood-forming cells in the bone marrow.

Damage to blood-forming cells can result in low white and red blood cell counts, which means you could be at risk for neutropenia and anemia. Neutropenia occurs when white blood cells are damaged and can put you at risk for infection. Anemia occurs when red blood cells are damaged and can cause symptoms such as fatigue, dizziness, weakness, and shortness of breath. Both neutropenia and anemia can become severe enough to require additional treatments or even hospitalization.

For Oncology Nurse Practitioner Cindy Cherry, when this happens to her patients, her alarm bells immediately go off. When patients come in and they have very low blood cell counts, thats the sick of the sick. Thats definitely the patient that I worry about the most, said Cherry.

Frequent communication with your care team may help to prevent worsening symptoms during treatment. Its important to speak up whenever you experience side effects, no matter the severity.

Despite swearing off chemotherapy, Dorothy had to endure another round of treatment after receiving her third cancer diagnosis in late 2020again, it was extensive-stage small cell lung cancer (ES-SCLC). However, this time was different than her first chemotherapy experience because she was recommended to a new oncologist who told her about a drug that wasnt available at the time of Dorothys previous SCLC diagnosis in 2019.

The drug her oncologist prescribed is called COSELA (trilaciclib), and it is available by prescription for people with an extensive-stage small cell lung cancer (ES-SCLC) diagnosis receiving certain types of chemotherapy.

Dorothys oncologist told her he wanted to try to protect her against some of the side effects of bone marrow suppression that she endured during her first experience with chemotherapy. Dorothy agreed to try COSELA and is thankful she decided to give chemotherapy treatment one more chance following her ES-SCLC diagnosis.

To help reduce the occurrence of low blood cell counts caused by bone marrow suppressionalso known as myelosuppressionCOSELA is given up to 4 hours before each chemotherapy treatment to help keep chemotherapy from damaging bone marrow while chemotherapy works to destroy the cancer cells.

Helping to protect cells in the bone marrow may help keep certain blood cell counts from dropping too lowwhich is what can cause side effects like neutropenia and anemia. This proactive protection of the bone marrow is what doctors call myeloprotection (my-low-proh-TEK-shun) and may help you stay on track with your scheduled treatment plan.

Ask your care team about myeloprotection during the next scheduled treatment. Your doctor will decide if COSELA is right for you.

Talking with your care team about any symptoms or side effects youre experiencing will help them determine the appropriate treatment for you. SCLC patient Dorothy T. wasnt afraid to discuss her symptoms with her doctor, which resulted in a treatment experience best suited for her. Its scary to think I almost decided to give up on treating my cancer rather than endure chemotherapy ever again, said Dorothy.

INDICATION

COSELA is a prescription medicine used to help reduce the occurrence of low blood cell counts caused by damage to bone marrow from chemotherapy. COSELA is used to treat adults taking certain chemotherapies (platinum/etoposide or topotecan) for extensive-stage small cell lung cancer.

COSELA is an injection for intravenous (IV) use given within 4 hours before chemotherapy.

IMPORTANT SAFETY INFORMATION

Do not take COSELA if you have had a serious allergic reaction to COSELA.

What are the possible serious side effects of COSELA?

Call your doctor or get medical care right away if you develop any of these symptoms or conditions.

Before taking COSELA, tell your doctor about all of your health conditions, including if you:

Tell your doctor about all the medications you are currently taking, including prescription and over-the-counter medicines, vitamins, supplements, and herbal supplements. COSELA and other medicines may affect each other. Keep a list of the medicines you take to show to your healthcare provider or pharmacist when you get a new medicine.

The most common side effects of COSELA include:

These are not all of the possible side effects of COSELA. Call your healthcare provider for medical advice about any side effects you may be experiencing. You are encouraged to report any negative side effects to G1 Therapeutics at1-800-790-G1TX, or to the FDA at 1-800-FDA-1088orwww.fda.gov/medwatch.

Please see the fullPrescribing Information.

References

G1 Therapeutics and the G1 Therapeutics logo, COSELA and the COSELA logo, G1 to One and the G1 to One logo are trademarks of G1 Therapeutics, Inc.

2022 G1 Therapeutics, Inc. All rights reserved. US-2100390 02/2022

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Starting Treatment for Small Cell Lung Cancer? Hear From an Oncology Nurse and a Cancer Patient. - Curetoday.com

- Primary Efficacy Endpoint Met Early in Renal Cell Carcinoma Group in Part B of Study

- Company to Host Conference Call and Webcast Today March 23, 10:00 am EST (2:00 pm GMT)

LEEDS, England, March 23, 2022--(BUSINESS WIRE)--4D pharma plc (AIM: DDDD, NASDAQ: LBPS), a pharmaceutical company leading the development of Live Biotherapeutic products (LBPs), a novel class of drug derived from the microbiome, today announces that in Part B of its signal finding study of MRx0518 in combination with MSDs anti-PD-1 therapy, KEYTRUDA (pembrolizumab) in patients with solid tumors that have progressed on a prior immune checkpoint inhibitor (ICI), the renal cell carcinoma (RCC) group has met its primary efficacy endpoint ahead of enrollment completion.

The ongoing study is being conducted in heavily pre-treated metastatic patients with solid tumors who have previously experienced clinical benefit on prior ICI therapy and subsequently developed progressive disease. The study is being conducted in collaboration with MSD (Merck & Co., Inc., Kenilworth, NJ, USA). The primary efficacy endpoint for Part B of the study is more than three out of 30 patients per tumor group achieving clinical benefit, defined as complete response, partial response, or stable disease for at least six months.

Part B of the study has to date enrolled 20 patients with RCC, of which four out of the first 16 evaluable patients have achieved clinical benefit, each having achieved at least 6 months of stable disease. To date, Part B of the study has enrolled 47 patients of up to a total of 120 patients with RCC, non-small cell lung cancer, bladder cancer, and head and neck squamous cell carcinoma. MRx0518 continues to be safe and well tolerated.

"Todays results in renal cell carcinoma, meeting the predefined primary efficacy endpoint early in this difficult to treat population, marks another important step forward for MRx0518 and the increasing importance of the microbiome in cancer treatment," commented Dr. Alex Stevenson, Chief Scientific Officer, 4D pharma. "Meeting the primary efficacy endpoint for this group is crucial for the future development of MRx0518, and these data are highly informative for our strategy going forward as we determine next steps in RCC."

Story continues

4D pharma intends to discuss next steps with partners and its Genitourinary Cancers Advisory Board regarding the development path of MRx0518 and a potentially pivotal study in patients with ICI-refractory RCC. 4D pharma will continue to recruit patients into the ongoing study of MRx0518 and Keytruda in RCC and the three tumor groups, with potential expansion into other types of ICI resistance.

KEYTRUDA is a registered trademark of Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA.

Conference Call & Webcast Information4D pharma will host a conference call and live webcast on Wednesday, March 23, 2022, at 10:00 am ET (2:00 pm GMT) to discuss the interim results of the Phase I/II study of the combination of MRx0518 and Keytruda for the treatment of renal cell carcinoma.

4D pharma management will be joined by key opinion leaders (KOLs) Dr. Petros Grivas, Associate Professor Clinical Research Division at the Fred Hutchinson Cancer Research Center, and Dr. Scott T. Tagawa, Professor of Medicine and Urology at Weill Cornell Medicine, both members of the 4D pharmas Genitourinary Cancers Advisory Board.

To access the live webcast, please visit the Events section of the 4D pharma website. To access audio only, please dial (866) 939-3921 (United States) and (678) 302-3550 (International) and reference Confirmation Number 50287940. A replay of the webcast and accompanying slides will be available on the 4D pharma website following the event.

About 4D pharma4D pharma is a world leader in the development of Live Biotherapeutics, a novel and emerging class of drugs, defined by the FDA as biological products that contain a live organism, such as a bacterium, that is applicable to the prevention, treatment or cure of a disease. 4D pharma has developed a proprietary platform, MicroRx, that rationally identifies Live Biotherapeutics based on a deep understanding of function and mechanism.

4D pharma's Live Biotherapeutic products (LBPs) are orally delivered single strains of bacteria that are naturally found in the healthy human gut. The Company has five clinical programs, namely a Phase I/II study of MRx0518 in combination with KEYTRUDA (pembrolizumab) in solid tumors, a Phase I study of MRx0518 in a neoadjuvant setting for patients with solid tumors, a Phase I study of MRx0518 in patients with pancreatic cancer, a Phase I/II study of MRx-4DP0004 in asthma, and Blautix in irritable bowel syndrome (IBS) which has completed a successful Phase II trial. A Phase I study of MRx0005 and MRx0029 in patients with Parkinsons disease is expected to commence in 2022. Additional preclinical-stage programs include candidates for CNS disease, immune-inflammatory conditions and cancer. The Company has a research collaboration with MSD (Merck & Co., Inc., Kenilworth, NJ, USA), to discover and develop Live Biotherapeutics for vaccines.

For more information, refer to https://www.4dpharmaplc.com.

Forward-Looking StatementsThis announcement contains "forward-looking statements." All statements other than statements of historical fact contained in this announcement, including without limitation statements regarding the efficacy of Live Biotherapeutics including MRx0518, the informative nature of the data for the Companys strategy, the Companys next steps with its partners and the potential expansion of the study into other types of ICI resistance, are forward-looking statements within the meaning of Section 27A of the United States Securities Act of 1933, as amended (the "Securities Act"), and Section 21E of the United States Securities Exchange Act of 1934, as amended (the "Exchange Act"). Forward-looking statements are often identified by the words "believe," "expect," "anticipate," "plan," "intend," "foresee," "should," "would," "could," "may," "estimate," "outlook" and similar expressions, including the negative thereof. The absence of these words, however, does not mean that the statements are not forward-looking. These forward-looking statements are based on the Company's current expectations, beliefs and assumptions concerning future developments and business conditions and their potential effect on the Company. While management believes that these forward-looking statements are reasonable as and when made, there can be no assurance that future developments affecting the Company will be those that it anticipates.

All of the Company's forward-looking statements involve known and unknown risks and uncertainties, some of which are significant or beyond its control, and assumptions that could cause actual results to differ materially from the Company's present expectations or projections. The foregoing factors and the other risks that could cause actual results to differ materially include risks relating to the efficacy of its Live Biotherapeutic drug candidates including MRx0518, the risk that the Company changes its expected strategy and plans, risk related to safety of investigational therapeutics, clinical development risk, and those additional risks and uncertainties described in the documents filed by the Company with the US Securities and Exchange Commission ("SEC"). The Company wishes to caution you not to place undue reliance on any forward-looking statements, which speak only as of the date hereof. The Company undertakes no obligation to publicly update or revise any of its forward-looking statements after the date they are made, whether as a result of new information, future events or otherwise, except to the extent required by law.

View source version on businesswire.com: https://www.businesswire.com/news/home/20220323005207/en/

Contacts

4D pharma Investor Relations ir@4dpharmaplc.com

Singer Capital Markets Nominated Adviser and Joint Broker Philip Davies / James Fischer (Corporate Finance) +44 (0)20 7496 3000Tom Salvesen (Corporate Broking)

Bryan Garnier & Co. Limited - Joint Broker Dominic Wilson +44 (0)20 7332 2500

Stern Investor Relations Julie Seidel +1-212-362-1200julie.seidel@sternir.com

Image Box Communications Neil Hunter / Michelle Boxall +44 (0)20 8943 4685neil@ibcomms.agency / michelle@ibcomms.agency

6 Degrees Lynne Dardanell +1-336-202-9689ldardanell@6degreespr.com

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4D pharma Announces Positive Interim Results from the Phase I/II Study of the Combination of MRx0518 and KEYTRUDA (pembrolizumab) for the Treatment of...

Open-label basket trial will assess the safety and efficacy of Zepzelca in patients with advanced urothelial carcinoma, large cell neuroendocrine carcinoma of the lung, or homologous recombination deficient tumors

DUBLIN, March 24, 2022 /PRNewswire/ -- Jazz Pharmaceuticals, Inc. (Nasdaq: JAZZ) today announced the first patient was enrolled in EMERGE-201, a Phase 2 clinical trial evaluating the safety and efficacy of Zepzelca(lurbinectedin)as a monotherapy in three cohorts of patients with advanced urothelial carcinoma, large cell neuroendocrine carcinoma of the lung, or homologous recombination deficient (HRD) tumors who have progressed on a platinum-containing regimen. EMERGE-201 will primarily assess patient objective response rates (ORR), according to the Response Evaluation Criteria in Solid Tumors (RECIST).

"Even with the rapid advancements in medical technology and care delivery across many tumor types over the last decade, there still remain many patients who continue to face unmet needs and experience a high burden of morbidity and mortality," said Arielle Heeke, M.D., breast medical oncologist at the Levine Cancer Institute and a primary investigator in the EMERGE-201 trial. "With the EMERGE-201 trial now underway, we look forward to seeing the potential clinical impact of Zepzelca on advanced solid tumor cancers, including HRD cancers, that have limited approved treatment options other than traditional chemotherapy. The trial will evaluate if this treatment can elicit tumor response based upon the underlying biology of these cancers and Zepzelca's novel method of action."

"This trial initiation is an exciting milestone for Zepzelca's clinical development program, as we seek to evaluate its clinical utility beyond treating small cell lung cancer," said Rob Iannone, M.D., M.S.C.E., executive vice president, global head of research and development of Jazz Pharmaceuticals. "Given Zepzelca triggers a cascade of events that can affect the activity of DNA binding proteins including transcription factors and DNA repair pathways we look forward to analyzing Zepzelca's activity in additional difficult-to-treat cancers where driver oncogenes are actively transcribed and DNA repair mechanisms are inefficient, such as urothelial carcinoma, large cell neuroendocrine carcinoma of the lung and HRD-positive tumors."

EMERGE-201 Trial Details

EMERGE-201 is a Phase 2, multicenter, open-label trial designed to assess the safety and efficacy of Zepzelca as a monotherapy in three cohorts of patients with solid tumors, who will receive3.2 mg/m2 doses of Zepzelca intravenously on day one of an every-three-week dosing cycle, until confirmed disease progression. The three cohorts are: patients with advanced urothelial carcinoma, large cell neuroendocrine carcinoma of the lung, or HRDtumors who have progressed on a platinum-containing regimen.

The primary objective is to determine Zepzelca's ability to improve patient outcomes, as measured by ORR. Key secondary endpoints include investigator-assessed progression free survival, time-to-response, duration of response, and disease control rate as assessed by RECIST, as well as overall survival in participants treated with Zepzelca. The trial is sponsored and is being conducted by Jazz Pharmaceuticals.

Approximately 20 sites in the U.S. will participate in this trial. Additional information about the trial, including eligibility criteria, can be found here.

About Zepzelca(lurbinectedin)

Zepzelcais an alkylating drug that binds guanine residues within DNA. This triggers a cascade of events that can affect the activity of DNA binding proteins, including some transcription factors, and DNA repair pathways, resulting in disruption of the cell cycle and eventual cell death.

TheFDAapprovedZepzelcaunder accelerated approval inJune 2020for the treatment of adult patients with metastatic SCLC with disease progression on or after platinum-based chemotherapy. The approval is based on overall response rate (ORR) and duration of response demonstrated in an open-label, monotherapy clinical study.In December 2021, Jazz and PharmaMar announced the initiation of LAGOON, a confirmatory Phase 3 clinical trial of Zepzelca for the treatment of patients with relapsed small cell lung cancer. If successful, LAGOON will serve as the confirmatory trial for Zepzelca to secure full approval in the U.S.

Zepzelca is a prescription medicine used to treat adults with small cell lung cancer that has spread to other parts of the body (metastatic) and who have received treatment with chemotherapy that contains platinum, and it did not work or is no longer working. Zepzelca is approved based on response rate and how long the response lasted. Additional studies will further evaluate the benefit of Zepzelca for this use. Zepzelca is not approved as part of a combination therapy or as a first-line maintenance treatment for patients with extensive-stage small cell lung cancer.

Important Safety Information for Patients

Before receiving ZEPZELCA, tell your healthcare provider about all of your medical conditions, including if you:

Females who are able to become pregnant:

Males with female partnerswho are able to become pregnant should use effective birth control during treatment with and for 4 months after your final dose of ZEPZELCA.

Females who are breastfeeding or plan to breastfeed. It is not known if ZEPZELCA passes into your breastmilk. Do not breastfeed during treatment with ZEPZELCA and for 2 weeks after your final dose of ZEPZELCA. Talk to your healthcare provider about the best way to feed your baby during treatment with ZEPZELCA.

Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements. Certain other medicines may affect how ZEPZELCA works.

What should I avoid while using ZEPZELCA?

Avoid eating or drinking grapefruit, or products that contain grapefruit juice during treatment with ZEPZELCA.

ZEPZELCA can cause serious side effects, including:

Tell your healthcare provider right away if you develop:

Tell your healthcare provider right away if you develop symptoms of liver problems including:

The most common side effects of ZEPZELCA include:

These are not all of the possible side effects of ZEPZELCA.

Call your doctor for medical advice about side effects. You are encouraged to report negative side effects of prescription drugs to the FDA. Visit http://www.fda.gov/medwatch or call 1-800-FDA-1088. You may also report side effects to Jazz Pharmaceuticals at 1-800-520-5568.

More information about Zepzelca, including Full Prescribing Information and Patient Information, is available here.

ZEPZELCA is a trademark of Pharma Mar, S.A. used by Jazz Pharmaceuticals under license.

About Urothelial Carcinoma

Urothelial carcinoma (UC) is the fourth most common tumor in the United States and is highly aggressive compared to other tumor types.[1] UC tumors often times spread locally, causing them to become more advanced and difficult to treat. Progressive disease after frontline chemotherapy is characterized by a short survival.[2]

About Large Cell Neuroendocrine Carcinoma

Large cell neuroendocrine carcinoma (LCNEC) is a rare type of cancer that can occur in the lungs and colon. There is no standard of care for LCNEC in lung cancer due to limited data on its pathology and clinical trials, making it a condition with great unmet needs in treatment and management.[3]

About Homologous Recombination Deficient-Positive Tumors

Homologous recombination deficiency (HRD) occurs across a variety of solid tumors including endometrial, biliary tract, urothelial, breast, pancreatic, gastric and esophageal. HRD hinders the body's essential mechanism that repairs damaged DNA in cells.[4] HRD tumors are seen in almost a fourth (17.4%) of tumors across 21 cancer types.

About Jazz Pharmaceuticals plc

Jazz Pharmaceuticals plc (NASDAQ: JAZZ) is a global biopharmaceutical company whose purpose is to innovate to transform the lives of patients and their families. We are dedicated to developing life-changing medicines for people with serious diseasesoften with limited or no therapeutic options. We have a diverse portfolio of marketed medicines and novel product candidates, from early- to late-stage development, in neuroscience and oncology. Within these therapeutic areas, we are identifying new options for patients by actively exploring small molecules and biologics, and through innovative delivery technologies and cannabinoid science.Jazz is headquartered in Dublin, Ireland and has employees around the globe, serving patients in nearly 75 countries. For more information, please visit http://www.jazzpharmaceuticals.com and follow @JazzPharma on Twitter.

Caution Concerning Forward-Looking Statements

This press release contains forward-looking statements, including, but not limited to, statements related to Jazz Pharmaceuticals' belief in the potential of Zepzelca to provide a potentially new therapeutic option for certain solid tumor types and other statements that are not historical facts. These forward-looking statements are based on Jazz Pharmaceuticals' current plans, objectives, estimates, expectations and intentions and inherently involve significant risks and uncertainties. Actual results and the timing of events could differ materially from those anticipated in such forward-looking statements as a result of these risks and uncertainties, which include, without limitation, effectively launching and commercializing new products; obtaining and maintaining adequate coverage and reimbursement for the company's products; delays or problems in the supply or manufacture of the company's products; and other risks and uncertainties affecting the company, including those described from time to time under the caption "Risk Factors" and elsewhere in Jazz Pharmaceuticals' Securities and Exchange Commission filings and reports (Commission File No. 001-33500), including Jazz Pharmaceuticals' Annual Report on Form 10-K for the year ended December 31, 2021 and future filings and reports by Jazz Pharmaceuticals. Other risks and uncertainties of which Jazz Pharmaceuticals is not currently aware may also affect Jazz Pharmaceuticals' forward-looking statements and may cause actual results and the timing of events to differ materially from those anticipated. The forward-looking statements herein are made only as of the date hereof or as of the dates indicated in the forward-looking statements, even if they are subsequently made available by Jazz Pharmaceuticals on its website or otherwise. Jazz Pharmaceuticals undertakes no obligation to update or supplement any forward-looking statements to reflect actual results, new information, future events, changes in its expectations or other circumstances that exist after the date as of which the forward-looking statements were made.

Media Contact:Kristin BhavnaniHead ofGlobal Corporate CommunicationsJazz Pharmaceuticals plcCorporateAffairsMediaInfo@jazzpharma.comIreland+353 1 637 2141U.S. +1 215 867 4948

Investors:Andrea N. Flynn, Ph.D.Vice President, Head, Investor RelationsJazz Pharmaceuticals plcinvestorinfo@jazzpharma.comIreland +353 1 634 3211U.S. +1 650 496 2717

References

1 Kim M, Jeong CW, Kwak C, et al. Are urothelial carcinomas of the upper urinary tract a distinct entity from urothelial carcinomas of the urinary bladder? Behavior of urothelial carcinoma after radical surgery with respect to anatomical location: a case control study. BMC Cancer 15, 149 (2015).2 Tanaka M, Sonpavde G. Diagnosis and management of urothelial carcinoma of the bladder. Postgrad Med. 2011 May;123(3):43-553 Lindsay CR, Shaw EC, Moore DA, et al. Large cell neuroendocrine lung carcinoma: Consensus statement from The British Thoracic Oncology Group and the Association of Pulmonary Pathologists. Br J Cancer. 2021;125:1210-1216. 4 Heeke AL, Pishvaian MJ, Lynce F, et al. Prevalence of homologous recombinationrelated gene mutations across multiple cancer types. JCO Precis Oncol. 2018;2018:PO.17.00286.

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SOURCE Jazz Pharmaceuticals plc

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Jazz Pharmaceuticals Announces First Patient Enrolled in EMERGE-201 Phase 2 Basket Trial Evaluating Zepzelca (lurbinectedin) Monotherapy in Patients...

Treatment for glioma has long relied on MRI imaging to track tumor markers and treatment response. But findings from a team at the University of Michigan Rogel Cancer Center, led by Carl Koschmann, M.D., pediatric neuro-oncologist at University of Michigan Health C.S. Mott Childrens Hospital and researcher with the Chad Carr Pediatric Brain Tumor Center, suggest a new method could provide additional data about tumor markers before changes appear on an MRI, indicating possible strategies to help clinicians address this aggressive form of cancer. The recent study appeared in Neuro-Oncology.

As part of a phase 1, multi-site clinical trial, Koschmanns team collected cerebrospinal fluid and plasma from patients with Diffuse Midline Glioma, or DMG, through blood draws and lumbar punctures over many months, collecting hundreds of samples. They wanted to track changes in cell-free tumor DNA as patients received treatment concurrent with the clinical trial.

We examined DNA floating in the plasma and CSF at various points in treatment and used a very sensitive machine called digital droplet polymerase chain reaction (ddPCR) to assess the fraction, called a variant allele fraction (VAF), of mutated DNA versus non-mutated, Koschmann said.

A higher VAF indicates more mutant DNA. Koschmanns team found that patients whose allele fraction went down after receiving the drug in the clinical trial took longer for the tumor to grow larger or relapse, data consistent with the teams expectations.

But the findings from the CSF also revealed a marker that hadnt been shown in this kind of study before, one that couldnt be found relying on MRI imaging alone.

When the treatment wasn't working and tumors were growing, as captured on an MRI, that didn't always correlate with the VAF rising and the tumor DNA getting worse, said Evan Cantor M.D., first author of the study who performed work at U-M and is now a pediatric neuro-oncology fellow at Washington University. More often, we saw a spike in the allele fraction in the tumor DNA before the tumor grew, on average about three to four months before.

Koschmann explains that this is the first study of its kind to collect serial CSF in a clinical trial for any type of glioma. It is very clear that DNA in the CSF can provide a lot of new information about the state of the tumor, he said.

The method falls under the genre of liquid biopsy, which Koschmann describes as an exciting new space in cancer care. For some types of cancer like leukemia, testing blood and bone marrow samples allows patients and physicians to follow the status of the disease and offers a thorough sense of treatment response. But for solid tumors, especially brain tumors, access to multiple metrics to measure tumor growth or response is not possible.

If you were to come into the clinic right now with a high-grade brain tumor, wed take an MRI and then make inferences from that imaging about how things are going. But theres a lot of handwaving about what it means, because its the only piece of data we have about how things are going, Koschmann said.

As these findings suggest, knowing that the increase in the allele fraction proceeds tumor growth, discovered through serial CSF sampling, could inform clinicians about different treatment needs much sooner than if only referencing MRIs. As a patient or patient family member, you don't want to wait until the MRI worsens to change course, Koschmann said.Having early information that you might need to adjust treatment is very valuable.

This study was conducted as an exploratory arm of a multisite phase 1 clinical trial across 15 institutions for pediatric patients with midline glioma tumors who have about a 12 to 18 month survival rate. Patients received a promising experimental therapy called ONC201 over the course of months and, in some cases, years.

Koschmann shared the findings from this study with the principal investigators planning the follow-up phase 2 clinical trial with ONC201 through the Pacific Neuro-Oncology Consortium (PNOC). Based on this, the investigators made serial spinal fluid collection standard for every patient on the clinical trial. Koschmann explains that this is one step closer to gathering enough data to see if this method can be integrated into future treatment options.

If this study validates our early findings, we should be ready to make this part of routine clinical care for patients with DMG even off trial. By rolling this out at trial sites across the country, were pressing the gas pedal on bringing this test to the clinic.

Paper cited: Serial H3K27M cell-free tumor DNA (cf-tDNA) tracking predicts ONC201 treatment response and progression in diffuse midline glioma, Neuro-Oncology.DOI: 10.1093/neuonc/noac030

Funding was provided by NIH/NINDS (K08-NS099427; R01-NS119231; R01NS124607; R01NS110572); Department of Defense (CA201129P1); the University of Michigan Chad Carr Pediatric Brain Tumor Center; the ChadTough Defeat DIPG Foundation; the DIPG Collaborative; Catching Up With Jack; The Pediatric Brain Tumor Foundation; Prayers from Maria; Yuvaan Tiwari Foundation; The Morgan Behen Golf Classic; and the Michael Miller Memorial Foundation. Clinical Trial was supported by Chimerix.

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Spinal fluid sampling used to track treatment response in pediatric glioma - Michigan Medicine