Category Archives: Gene therapy

Docket Number: FDA-2019-D-5392 Issued by:

Guidance Issuing Office

Office of Medical Products and Tobacco, Center for Biologics Evaluation and Research

This guidance provides FDAs current thinking on determining sameness of human gene therapy products under FDAs orphan drug regulations for the purpose of orphan-drug designation and orphan-drug exclusivity. This guidance is intended to assist stakeholders, including industry and academic sponsors who seek orphan-drug designation and orphan-drug exclusivity, in the development of gene therapies for rare diseases. This guidance focuses specifically on factors that FDA generally intends to consider when determining sameness for gene therapy products and does not address sameness determinations for other types of products.

You can submit online or written comments on any guidance at any time (see 21 CFR 10.115(g)(5))

If unable to submit comments online, please mail written comments to:

Dockets ManagementFood and Drug Administration5630 Fishers Lane, Rm 1061Rockville, MD 20852

All written comments should be identified with this document's docket number: FDA-2019-D-5392 .

01/28/2020

Continue reading here:
Interpreting Sameness Gene Therapy Products Orphan Drug Regulations - FDA.gov

Innovative treatments have turned the tables somewhat in the battle against cancer but one stumbling block appears to be pricing. CAR-T cell therapy can cost more than $1.5 million including the $475,000 cost of the drug (in this case, Kymriah from Novartis).

We are seeing that price is becoming a barrier because if you can imagine, hundreds of thousands of people all suddenly becoming eligible for CAR-T, there isnt enough money in the healthcare system to pay for that, said Paul Wotton, CEO of Obsidian Therapeutics, based in Cambridge, Massachusetts.

In a recent interview in San Francisco, Wotton and another biopharma executive pointed to a solution to the price conundrum: an off-the-shelf approach.

To clarify, to date the approved CAR-T therapies involve cells from the patients own body that are re-engineered and placed back into the body in order to overpower and kill the cancerous growth. While revolutionary, this is not only a cumbrous process but also expensive.

Now, some companies are going the route of using donor cells to develop their own treatment regimens. These are known as allogeneic therapies.

Wugen Therapeutics is one such company that is taking an allogeneic approach to CAR-T therapy. Based in St. Louis Missouri with technology developed out of Washington University, the company targets T-cell malignancies in leukemia and lymphoma, said Ayman Kabakibi, vice president of research and development. In a recent interview, he explained that so far CAR-T therapies have focused on B-cell malignancies because it is less difficult to target B-cell malignancies with a T-cell.

The reason is that if you go back to the basics of CAR-T you are trying to put a receptor (CAR) on the normal T-cell to allow it to recognize another antigen or marker on the tumor cell and when that interaction happens, two things happen the T-cell will proliferate and make more daughter cells and thats why we call it a living drug, Kabakibi explained. And the other thing that happens is that it secretes toxins that kill the tumor cells. Well, you can do that more easily for B cells because the antigens are not shared between the two.

But at Wugen, the company is using re-engineeerd normal T-cells to target cancerous T-cells and certain adjustments need to be made so that the cells dont end up killing each other.

So what we do is that we take the T-cells and we remove the antigen that we are targeting on the cancer cell using CRISPR CAS technology, he said. We take T-cells from a normal person. We eliminate that marker and then we put another gene to make it stress the receptor that it will recognize.

Why not take T-cells from the patients own body?

One reason is that in many cases by the time patients land on CAR-T therapy, they may have already undergone several rounds of other treatments that may have compromised the health of a normal T-cell.

Because the patient has had so many chemotherapies the chances of getting a healthy T-cell are actually pretty low, he said. There are 20-30 percent of patients that go for CAR-T therapy and they get into the clinic and get their blood taken out and then it takes six weeks to generate autologous CAR-T therapy but they cant do it because theres not enough starting material, not enough healthy cells.

This approach of using donor T-cells gets around this problem but Kabakibi believes that it also solves the problem of the skyrocketing cost of CAR-T therapies.

You dont get the economies of scale [with CAR-T using autologous approach,] he said. Thats why you have to be able to generate hundreds of doses and not from the patient, but from a normal patient. You need an off-the-shelf, allogenic version. You take the cells from a normal person and generate a hundred vials that could be shipped overnight to a patient and then that person can be treated in a few days.

Wotton, the CEO of Obsidian Therapeutics, echoed Kabakibi.

You have to find a way to drive down that cost of goods. The way science is going to address that I think is to have off-the-shelf approaches where you can grow billions of cells from a single cell, engineer it to be able to get it to all of us to treat whatever it is we are suffering from, Wotton said. It is much better to build that scale of manufacturing rather than on a patient by patient basis.

Obsidian Therapeutics has developed what it calls destabilizing domain technology to be able to more precisely dose cell and gene therapies.

We are pioneering controllable cell and gene therapies using technology that came out of Stanford University, Wotton said. So in a nutshell, if you give somebody gene therapy today, to produce a particular protein in the body you actually have no idea how much of that protein is going to express. And the same in the case of a CAR-T cell to patients, you actually dont know how many of those cells are going to survive, how quickly they are going to proliferate so being able to dose cell and gene therapies in the same way you can dose a small molecule would be extremely useful.

Obsidianhas a partnership with Celgene through which Celgene can in-license global rights to cell therapy product candidates developed by Obsidian that incorporate destabilizing domain-regulated interleukin 12 or CD40L to fight cancer. Obdisial is using an allogeneic approach.

Our goal in life is to turn cell therapy into the first line of treatment instead of the last line of treatment, Wotton said. The only way you are going to be able to do that is to provide a cell therapeutic that is off-the-shelf, readily available and easy for patients to access, which is actually the approach that we are trying to take.

However, he added that there has to be a balance between cost and value when it comes to novel treatment.

Kabakibi of Wugen Therapeutics agreed.

If you are generating a 100 vials of CAR-T cells, is the price going to drop by 100 percent? Unlikely, he said. I think some therapies will never be as inexpensive as a pill.

Photo: champc, Getty Images

Visit link:
Makers of novel cell/gene therapy say off-the-shelf approach only way to solve pricing woes - MedCity News

Pfizer aims to be the third big pharma with a significant presence in gene therapy. Its plans to initiate this year three Phase 3 trials targeting mutation-driven blood and muscular diseases would make it a large player in this cutting-edge area of medicine.

The difference between Pfizer and its Swiss rivals Novartis and Roche is that its treatments for muscular dystrophy and hemophilia do not look like they will be the first to market. With hopes that gene therapy could be a one-and-done treatment, arriving second could put Pfizer at a disadvantage if eager patients rush for curative therapies.

Having spun of its off-patent drugs business, the pharma is now trying to talk up the "new Pfizer." Its gene therapies are among seven pipeline projects that it cited Tuesday during its year-end earnings call as critical to its strategy of becoming a more innovation-focused company.

Company executives weren't, however, asked to answer how Pfizer views the emerging gene therapy competition. BioMarin Pharmaceutical looks set to get to the market earlier in hemophilia A than Pfizer, while Uniqure in hemophilia B and Sarepta Therapeutics in Duchenne muscular dystrophy appear ahead.

Pfizer's hemophilia A project, the Sangamo Therapeutics-originated SB-525, is up against BioMarin's valrox, which has been submitted to the Food and Drug Administration for an approval decision later this year.

In hemophilia B, fidanacogene elaparvovec, licensed from Roche subsidiary Spark Therapeutics, is in a neck-and-neck race with UniQure's etranacogene dezaparvovec in Phase 3 testing. Duchenne research, meanwhile, is led by Sarepta, which is launching a Phase 3 trial of its drug this year, putting Pfizer's at a disadvantage.

Other than announcing its intent to launch Phase 3 trials in hemophilia A and Duchenne, Pfizer didn't provide much more detail about these clinical programs. Mikael Dolsten, Pfizer's chief scientific officer, said more could be revealed about the DMD program at an upcoming research & development day.

Progress on that project had been delayed after one patient was hospitalized with kidney complications, but Dolsten said trial investigators had dosed additional patients. The Phase 2 will wrap up this spring, and the new data and longer follow-up will help guide a Phase 3 trial design, the company said.

Dolsten also described the hemophilia A project as having a 'best-in-class profile," even though BioMarin's valrox has impressed hematologists with its ability to increase expression of a key blood-clotting protein.

In addition, he said the company hopes it can bring one new gene therapy into its pipeline per year.

Building its drug development portfolio is one reason why the company has chosen not to buy back shares, said CEO Albert Bourla.

He pointed to the company's need in the past to buy back shares to support their valuation because of revenue declines, but now he said the company is in a different strategic position.

"The company is going to have a best-in-class revenue growth story," he said. "We can use the capital to invest in good Phase 2, Phase 3 assets to grow our pipeline."

Read the original post:
Pfizer lays out gene therapy aspirations - BioPharma Dive

DUBLIN, Jan. 28, 2020 /PRNewswire/ -- The "Gene Therapy - Technologies, Markets & Companies" report from Jain PharmaBiotech has been added to ResearchAndMarkets.com's offering.

Research and Markets Logo

The markets for gene therapy have been difficult to estimate as there only a few approved gene therapy products. Gene therapy markets are estimated for the years 2018-2028.

The estimates are based on the epidemiology of diseases to be treated with gene therapy, the portion of those who will be eligible for these treatments, competing technologies and the technical developments anticipated in the next decades. In spite of some setbacks, the future for gene therapy is bright. The markets for DNA vaccines are calculated separately as only genetically modified vaccines and those using viral vectors are included in the gene therapy markets

Profiles of 193 companies involved in developing gene therapy are presented along with 266 collaborations. There were only 44 companies involved in this area in 1995. In spite of some failures and mergers, the number of companies has increased more than 4-fold in 2 decades. These companies have been followed up since they were the topic of a book on gene therapy companies by the author of this report. John Wiley & Sons published the book in 2000 and from 2001 to 2003, updated versions of these companies (approximately 160 at mid-2003) were available on Wiley's web site. Since that free service was discontinued and the rights reverted to the author, this report remains the only authorized continuously updated version on gene therapy companies.

Gene therapy can be broadly defined as the transfer of defined genetic material to specific target cells of a patient for the ultimate purpose of preventing or altering a particular disease state.

Genes and DNA are now being introduced without the use of vectors and various techniques are being used to modify the function of genes in vivo without gene transfer. If one adds to this the cell therapy particularly with use of genetically modified cells, the scope of gene therapy becomes much broader.

Gene therapy can now combined with antisense techniques such as RNA interference (RNAi), further increasing the therapeutic applications. This report takes broad overview of gene therapy and is the most up-to-date presentation from the author on this topic built-up from a series of gene therapy report written by him during the past decade including a textbook of gene therapy and a book on gene therapy companies. This report describes the setbacks of gene therapy and renewed interest in the topic

Gene therapy technologies are described in detail including viral vectors, nonviral vectors and cell therapy with genetically modified vectors. Gene therapy is an excellent method of drug delivery and various routes of administration as well as targeted gene therapy are described. There is an introduction to technologies for gene suppression as well as molecular diagnostics to detect and monitor gene expression. Gene editing technologies such as CRISPR-Cas9 and CAR-T cell therapies are also included.

Clinical applications of gene therapy are extensive and cover most systems and their disorders. Full chapters are devoted to genetic syndromes, cancer, cardiovascular diseases, neurological disorders and viral infections with emphasis on AIDS. Applications of gene therapy in veterinary medicine, particularly for treating cats and dogs, are included.

Research and development is in progress in both the academic and the industrial sectors. The National Institutes of Health (NIH) of the US is playing an important part. As of 2016, over 2050 clinical trials were completed, were ongoing or had been approved worldwide. A breakdown of these trials is shown according to the geographical areas and applications.

Since the death of Jesse Gelsinger in the US following a gene therapy treatment, the FDA has further tightened the regulatory control on gene therapy. A further setback was the reports of leukemia following the use of retroviral vectors in successful gene therapy for adenosine deaminase deficiency. Several clinical trials were put on hold and many have resumed now. Three gene medicines have been approved by the FDA. The report also discusses the adverse effects of various vectors, safety regulations and ethical aspects of gene therapy including gene editing and germline gene therapy.

Story continues

See original here:
Gene Therapy Industry Insights and Outlook to 2028 - Genetic Disorders, Cancer, Neurological Disorders, Cardiovascular Disorders, and Viral Infections...

SAN DIEGO, Jan. 28, 2020 (GLOBE NEWSWIRE) -- Otonomy, Inc.(Nasdaq: OTIC), a biopharmaceutical company dedicated to the development of innovative therapeutics for neurotology, today announced preclinical results from the companys gene therapy collaboration with Applied Genetic Technologies Corporation (Nasdaq: AGTC) focused initially on treating GJB2 deficiency for congenital hearing loss, and preclinical results demonstrating the therapeutic potential of a class of compounds being evaluated for otoprotection against cisplatin-induced hearing loss (CIHL). These results were presented during the ongoing Association for Research in Otolaryngology (ARO) 43rd Annual MidWinter Meeting being held in San Jose, California.

Together with our strategic partner, AGTC, we are encouraged by these initial preclinical results that demonstrate our ability to express a gene of interest in the target cells relevant to the treatment of congenital hearing loss due to GJB2 deficiency," said David A. Weber, Ph.D., president and chief executive officer of Otonomy. Also, the preclinical results presented for our OTO-510 program highlight the therapeutic potential of a novel class of cisplatin-binding molecules for protection against CIHL and the higher potency of these agents versus other molecules currently in clinical development.

Preclinical Results for GJB2 Gene Therapy Collaboration

In October 2019, Otonomy and AGTC announced a strategic collaboration to co-develop and co-commercialize an AAV-based gene therapy to restore hearing in patients with sensorineural hearing loss caused by a mutation in the gap junction protein beta 2 gene (GJB2) -- the most common cause of congenital hearing loss. The joint presentation by Otonomy and AGTC at ARO provided initial demonstration that a gene of interest can be expressed in support cells of the cochlea, which are the relevant target cells for treating GJB2 deficiency, using novel and proprietary AAV capsids. Furthermore, these studies identified several capsids with favorable tropism and gene expression level in support cells compared to previously reported capsids used in the field. Importantly, none of the novel AAV capsids evaluated for further development exhibited signs of cellular toxicity.

Preclinical Results for OTO-510 Otoprotection Program

Cisplatin is a potent chemotherapeutic agent that is widely used to treat a variety of cancers in adults and children. Unfortunately, the administration of cisplatin is commonly associated with severe adverse effects including CIHL that is progressive, bilateral and irreversible. At ARO, Otonomy presented preclinical results demonstrating varying degrees of otoprotection against CIHL for several different classes of therapeutic agents. In particular, a novel proprietary class of agents that potently bind to cisplatin demonstrated greater otoprotection than anti-oxidant and anti-apoptotic molecules, and increased potency relative to other cisplatin-binding molecules currently in clinical development. These results highlight the therapeutic potential of Otonomys novel otoprotectant agents as the basis for the OTO-510 program for CIHL.

About Otonomy

Otonomy is a biopharmaceutical company dedicated to the development of innovative therapeutics for neurotology. The company pioneered the application of drug delivery technology to the ear in order to develop products that achieve sustained drug exposure from a single local administration. This approach is covered by a broad patent estate and is being utilized to develop a pipeline of products addressing important unmet medical needs including Mnires disease, hearing loss, and tinnitus. For additional information please visit http://www.otonomy.com.

Cautionary Note Regarding Forward Looking Statements

This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. Forward-looking statements generally relate to future events or the future financial or operating performance of Otonomy. Forward-looking statements in this press release include, but are not limited to expectations regarding the potential benefits, development activity and advancement of preclinical programs; the potential benefits of and activity under the collaboration agreement between AGTC and Otonomy, including but not limited to development activity; and statements by Otonomys president and CEO. Otonomys expectations regarding these matters may not materialize, and actual results in future periods are subject to risks and uncertainties. Actual results may differ materially from those indicated by these forward-looking statements as a result of these risks and uncertainties, including but not limited to: Otonomys limited operating history and its expectation that it will incur significant losses for the foreseeable future; Otonomys ability to accurately forecast financial results; Otonomys ability to obtain additional financing; Otonomys dependence on the regulatory success and advancement of its product candidates; the uncertainties inherent in the clinical drug development process, including, without limitation, Otonomys ability to adequately demonstrate the safety and efficacy of its product candidates, the nonclinical and clinical results for its product candidates, which may not support further development, and challenges related to patient enrollment in clinical trials; Otonomys ability to obtain regulatory approval for its product candidates; the risks of the occurrence of any event, change or other circumstance that could give rise to the termination of the collaboration agreement between AGTC and Otonomy; the risks of the occurrence of any event, change or other circumstance that could impact Otonomys ability to repay or comply with the terms of the loan provided by Oxford Finance LLC; side effects or adverse events associated with Otonomys product candidates; Otonomys ability to successfully commercialize its product candidates, if approved; competition in the biopharmaceutical industry; Otonomys dependence on third parties to conduct nonclinical studies and clinical trials; Otonomys dependence on third parties for the manufacture of its product candidates; Otonomys dependence on a small number of suppliers for raw materials; Otonomys ability to protect its intellectual property related to its product candidates in the United States and throughout the world; expectations regarding potential therapy benefits, market size, opportunity and growth; Otonomys ability to manage operating expenses; implementation of Otonomys business model and strategic plans for its business, products and technology; and other risks. Information regarding the foregoing and additional risks may be found in the section entitled "Risk Factors" in Otonomys Quarterly Report on Form 10-Q filed with the Securities and Exchange Commission (the "SEC") on November 5, 2019, and Otonomys future reports to be filed with the SEC. The forward-looking statements in this press release are based on information available to Otonomy as of the date hereof. Otonomy disclaims any obligation to update any forward-looking statements, except as required by law.

Contacts:

Media Inquiries:Spectrum ScienceChlo-Anne RamseyVice President404.865.3601cramsey@spectrumscience.com

Investor Inquiries:Westwicke ICRRobert H. UhlManaging Director858.356.5932robert.uhl@westwicke.com

See the original post here:
Otonomy Presents Preclinical Results for GJB2 Gene Therapy Collaboration and Cisplatin Otoprotection Program - BioSpace

RESEARCH TRIANGLE PARK, N.C., Jan. 29, 2020 (GLOBE NEWSWIRE) -- Asklepios BioPharmaceutical, Inc. (AskBio), a clinical-stage adeno-associated virus (AAV) gene therapy company, today introduced AskFirst, its collaborative program for patients and their families who may benefit from its advances in gene therapy research and potential curative therapies. The purpose of the program is to keep patients and families informed, ensure safety information is accurately communicated, and provide support when participating in clinical trials.

AskBio was founded with a patient-focused mission to develop transformative genetic medicines for patients with serious diseases previously considered untreatable, said Martin Childers, DO, PhD, Chief Medical Officer at AskBio. This patient-centered approach is at the heart of our AskFirst program that embraces the voice of patients and their families and puts their welfare first. We support the important work of patient advocacy organizations that play an essential role in advancing gene therapy.

To lead the AskFirst program, Matthew Alsante has joined the company as the director of patient advocacy. He brings more than a decade of experience within patient advocacy organizations and most recently served as CEO of the National Pancreas Foundation. Prior to that, Matthew was the executive director of the Sarcoma Foundation of America.

I am extremely excited about this opportunity to develop and grow AskFirst, said Matthew. AskBio has a long history of commitment to the patient community, and Im honored to build upon that foundation and provide an external link to the important, life-changing work that is happening here. The patient voice is vital to everything we do. Its my job to bring that into every aspect of gene therapy development, because we cant do it without the incredible partnerships we have with patients and the patient community.

For questions about AskFirst, please email us at AskFirst@askbio.com. You can also follow our advocacy news on Facebook or sign up for our patient newsletter at https://www.askbio.com/patient-advocacy.

About AskBioFounded in 2001, Asklepios BioPharmaceutical, Inc. (AskBio) is a privately held, clinical-stage gene therapy company dedicated to improving the lives of children and adults with genetic disorders. AskBios gene therapy platform includes an industry-leading proprietary cell line manufacturing process called Pro10 and an extensive AAV capsid and promoter library. Based in Research Triangle Park, North Carolina, the company has generated hundreds of proprietary third-generation AAV capsids and promoters, several of which have entered clinical testing. An early innovator in the space, AskBio holds more than 500 patents in areas such as AAV production and chimeric and self-complementary capsids. AskBio maintains a portfolio of clinical programs across a range of neurodegenerative and neuromuscular indications with a current clinical pipeline that includes therapeutics for Pompe disease, limb-girdle muscular dystrophy 2i/9R and congestive heart failure, as well as out-licensed clinical indications for hemophilia (Chatham Therapeutics acquired by Takeda) and Duchenne muscular dystrophy (Bamboo Therapeutics acquired by Pfizer). Learn more at https://www.askbio.com or follow us on LinkedIn.

A photo accompanying this announcement is available at https://www.globenewswire.com/NewsRoom/AttachmentNg/e2f27a2a-e7c1-4ca5-b0d9-7f47b43edd53

Matthew Alsante - Director, Patient Advocacy at AskBio

Matthew Alsante has joined AskBio to lead its AskFirst patient advocacy program. He most recently served as CEO of the National Pancreas Foundation.

Read the original:
AskBio Launches AskFirst Patient Advocacy Program to Educate and Support Participants in Gene Therapy Clinical TrialsMatthew Alsante to Lead Program...

Krystal Biotech is confident enough about its pipeline of candidates of gene therapies for treating skin diseases that has started work on a new commercial manufacturing facility. It has even given it a name.

The Pittsburgh, Pennsylvania-based Kystal broke ground Friday on a 100,000-square-foot manufacturing facility that it is calling Astra. A spokesman for the company said in an email today the biotech expects to invest $75 million to $90 million on the facility, which is a modular enlargement of its existing facility in Pittsburgh.

The plant is slated to be complete in 12 to 15 months and will initially employ 75 workers, with the potential for 200 when it is fully operational, the company said.

RELATED: With phase 2 update, Krystal Biotech eyes phase 3 for rare skin disease gene therapy

Biologics manufacturing is a complex science and is a competitive advantage for Krystal Biotech," Krystal CEO Krish S. Krishnan said in a statementThe success with our first GMP facility, Ancoris, gives us the experience and confidence to have Astra be functionally ready in time for the anticipated launch of our lead therapeutic, B-VEC (previously KB103)."

In its earnings reportin November, the company said that it was reassured during a meeting with the FDA about manufacturing controls that it has a scalable GMP commercial process in place.It intends to make the clinical material for an upcoming phase 3 trial of B-VEC at its Ancoris facility and anticipates starting the trial in Q1 2020.

B-VEC is being developed to treat the most severe form of epidermolysis bullosa, a disease that is usually diagnosed in infancy andthat results from mutations in the COL7A1 gene.Babies born with the more severe form will have widespread blistering and areas where there is no skin. The disease can lead to vision loss, difficulty eating due to blistering and scarring in the mouth and esophagus and other issues.

RELATED: Krystal files for IPO to move gene therapies into clinic

It reported last fall that in its phase 2 trial,five out of six wounds treated with B-VEC closed 100% in an average of 23 days.

The FDA also has fast-tracked Krystals second product candidate, KB105, an HSV-1 based gene therapy engineered to deliver a human transglutaminase-1 (TGM1) gene to patients with TGM1-deficient autosomal recessive congenital ichthyosis (ARCI).

The company, which raised about $45 million in a 2017 IPO, reported cash equivalents and short-term investments of $203.2 million at the end of its third quarter on September 30, 2019.It had a net loss of $0.25 a share compared with a $0.26 per share loss in the same quarter of 2018.

See original here:
Krystal Biotech investing up to $90M on facility for its gene therapies - FiercePharma

Genetic medicines and cellular therapies have an enormous potential to treat, and possibly cure, currently untreatable diseases. Nonetheless, it's important for investors to remember that "simpler" treatment options won't become obsolete just because gene therapy, gene editing, and immunotherapy approaches are becoming feasible.

Investors are hoping that the 'simple is better' approach proves true for Codexis (NASDAQ:CDXS).The company's first drug candidate, the enzyme-based CDX-6114, is being developed to treat a rare disease called phenylketonuria (PKU). Can the simpler approach of Codexis compete with a growing list of gene therapies that are also targeting the disease?

Image source: Getty Images.

Codexis isn't a biopharmaceutical company. It has developed a platform for engineering enzymes, which are complex molecules that power virtually all biological processes in living cells. Enzymes can also be added to industrial processes, health diagnostics, and consumer products to reduce energy consumption, lower input requirements, improve functionality, and eliminate toxic wastes.

Today, the company generates most of its revenue from three sources: selling enzymes that improve drug manufacturing processes, selling enzymes that improve the manufacturing process for a zero-calorie sweetener ingredient from Tate & Lyle, and selling licenses to its enzyme engineering software platform. But Codexis is also eyeing a large opportunity in developing novel therapeutics.

In late 2017, Codexis and Nestle Health Science, owned by Nestle, entered into an agreement to develop rare-disease drug candidates. The goal is to engineer enzymes that can be administered orally, rather than injected or given intravenously, which would provide a significant advantage in cost and convenience relative to treatments for many rare diseases.

Designing medicines that can be taken orally may not sound very novel, but enzyme-based treatments are typically degraded as they journey through the gastrointestinal (GI) tract. That requires enzymatic medicines to be administered subcutaneously, which can trigger severe allergic reactions and doesn't efficiently deliver them to the liver, where they're most effective. Therefore, Codexis must engineer enzymes that are stable enough to make it through the GI tract so they can be transported into the liver -- a capability uniquely accessible to Codexis.

The first asset to advance into clinical trials was the experimental PKU treatment called CDX-6114. Individuals born with PKU have a nonfunctioning copy of the enzyme phenylalanine hydroxylase (PAH) that metabolizes the amino acid phenylalanine (Phe). When Phe accumulates to dangerous levels, it can cause significant intellectual disabilities in newborns and mental impairments in adults. Individuals must follow a strict (and expensive) diet that limits daily protein intake to just five grams and avoids the artificial sweetener aspartame, which breaks down into Phe. CDX-6114 was designed to help individuals metabolize Phe and live a normal lifestyle.

In early 2019, Nestle Health Science, which sells many nutritional products for PKU patients, exercised an option granting it exclusive rights to develop and commercialize CDX-6114. Codexis is eligible to receive up to $85 million in remaining development and approval milestones, up to $250 million in revenue milestones, and royalties on sales.

For comparison, Codexis generated $44 million in the first nine months of 2019. While the industrial business is growing, achieving success with the therapeutic pipeline could provide a significant boost. Will gene therapies stand in the way?

Image source: Getty Images.

The hypothesis supporting the collaboration between Codexis and Nestle Health Science is pretty simple to understand: Many rare diseases are caused when individuals fail to make a specific functioning enzyme, so treatments that provide a working copy could prove valuable. Of course, that's the exact hypothesis supporting the industry's pursuit of genetic medicines.

Whereas Codexis wants to provide an enzyme substitute through an orally available drug, a gene therapy aims to provide direct replacement of an enzyme by potentially fixing the genetic error at the root of a disease.

It might be tempting to think that gene therapy is the ideal solution for PKU, but not every gene therapy will succeed in providing a cure. If a gene therapy only partially succeeds in replacing adequate levels of the gene responsible for producing the PAH enzyme, then individuals might still be dependent on strict diets and imperfect treatment options. Simply put, barring the successful development of a curative gene therapy, the enzyme-based approach of Codexis and Nestle Health Science could be a competitive option.

It's not much of a competition at the moment, as there's not much to compare. CDX-6114 is being studied in a phase 1b study, while early-stage results for gene therapies have been unimpressive or non-existent.

Company

PKU Drug Candidate

Results

Codexisand Nestle Health Science

CDX-6114 (enzymatic)

Phase 1a trial: well tolerated at all four dose levels in 32 healthy volunteers, but not tested in PKU patients

Homology Medicines (NASDAQ:FIXX)

HMI-102 (gene therapy)

Phase 1/2 trial (ongoing): two individuals with PKU receiving low-dose showed no reduction in Phe at three months, one individual receiving high-dose achieved a reduction in Phe

BioMarin (NASDAQ:BMRN)

BMN 307 (gene therapy)

Expects to initiate phase 1/2 trial in the United Kingdom in early 2020

Data sources: Codexis, Homology Medicines, and BioMarin.

Despite the early-stage nature of the industry's pipeline, the opportunity is large and the bar is relatively low.

Individuals with PKU currently have two main drug options: Kuvan and Palynziq. The two drugs, both sold by BioMarin, generated combined revenue of $396 million in the first nine months of 2019. But they're only partial solutions.

Kuvan is a coenzyme that can help to break down Phe, but it only works for individuals with milder PKU and comes with a relatively long list of side effects. It still generated $341 million in revenue in the first nine months of 2019.

Palynziq is a newer therapy. It's a substitute to working PAH enzymes required to metabolize Phe, but the drug can take up to 12 months to begin working and triggers significant side effects in most people. It comes with a black-box warning for severe allergic reactions (observed in 9% of individuals in clinical trials), requires daily injections, and costs $192,000 per year. While doctors have been generally impressed with results for patients that stick with treatment, there's much room for improvement.

Codexis is hoping that CDX-6114 can provide a convenient and safe enzyme-based treatment option for individuals with PKU. If the asset demonstrates promising clinical results in an ongoing phase 1b trial, then it could begin to factor into the pharma stock's price and the company's market valuation. After all, analysts expect Palynziq to generate over $1 billion in peak annual sales despite the drug's inconveniences and safety issues, and Codexis is valued at just $1 billion today.

However, investors do need to keep track of genetic medicines in development at Homology Medicines, BioMarin, and any other companies that throw their hats into the ring (RNA interference seems uniquely suited for a PKU treatment, but no such drugs are in development yet). If genetic medicines demonstrate a consistent safety profile and provide a cure for most individuals with PKU in early clinical trials, then CDX-6114 might have its market potential severely reduced before it even leaves the clinic. If genetic medicines only provide partial solutions, then the details and nuance might determine which approach, if any, will dominate the market.

The next batch of results from each company is likely to be available before the end of 2020, which means investors will learn quite a bit about the shape of the competitive landscape soon.

See the rest here:
Codexis Is Chasing a Blockbuster Opportunity. Can It Compete With Gene Therapies? - Motley Fool

At the Bio International Convention held last year in Philadelphia, The Discovery Labs announced it was opening 1.6 million square feet of coworking space and collaborative labs for healthcare, life sciences and tech companies out of GlaxoSmithKlinesformer campus in King of Prussia.

About half a year later, nearly all its square footage has been accounted for, Audrey Greenberg, executive managing director of the Discovery Labs, told Technical.ly.

Included is a big get for the region: The Discovery Labs and Deerfield Management Company have formed The Center for Breakthrough Medicines, a contract development and manufacturing organization and specialty investment company, the Discovery Labs announced this week.

The Center for Breakthrough Medicines leased 680,000 square feet of Discovery Labs facility to provide pre-clinical through commercial manufacturing of cell and gene therapies, including process development, plasmid DNA, viral vectors, cell banking, cell processing and support testing capabilities.

Its goal is to to alleviate the critical lack of capacity that is preventing patients from accessing critically needed cell and gene therapies, Discovery Labs said.

Today brilliant scientists are advancing an unprecedented number of gene and cell therapy drug candidates. The real tragedy, however, is a scarcity of manufacturing know-how, which is complex and expensive, said Alex Karnal, partner and managing director of Deerfield Management and a board member of the Discovery Labs, in a statement. It is hoped that the Center for Breakthrough Medicines will help realize the promise of cell and gene therapies in time to treat the many patients who need them.

TheCenter for Breakthrough Medicines has initiated a substantial hiring effort, with plans to hire more than 2,000 team members within the next 30 months in positions like Ph.D. scientists, manufacturing experts, lab technicians and support staff.

Greenberg called the company an end-to-end solution for companies that are looking to manufacture their solutions and products.

There wasnt really space for that to happen, and were in a biotech epicenter, she said. Companies can grow within our space.

An early rendering of The Discovery Labs. (Courtesy image)

First leases within the 1.6 million square feet across campus will likely be taken up by 10 to 20 companies in the first quarter of 2020. Many, including the Center for Breakthrough Medicines, will move into the space in Q3 or Q4 of 2020, after renovations are complete and labs are outfitted to each companys needs.

The campus is also getting a biotech incubator, Unite IQ, which will offer space to emerging life sciences startups with resources needed to initiate business operations. Unite IQ tenants will be able to use the discovery, development, testing and manufacturing capabilities of the Center for Breakthrough Medicines and tech transfer from research lab to large-scale production.

Currently, Philadelphia is home to the only Discovery Labs campus, but the company is looking toward expanding with locations on the West Coast, in Asia and in Europe.

The region is continuously growing as a hub for life sciences, andGreenberg cited King of Prussias proximity to top cell and gene therapy talent, area hospitals and patient pools as important to the Discovery Labs. Also important, she noted, was access to the Philadelphia International Airport (and its supply-chain abilities with cold storage function for transporting cell therapies).

The work is extremely important to Greenberg personally, she said.

Theres an immediacy to this work, in this industry thats working on cures for patients who are dying every day, she said. To me, this work is doing well by doing good.

View original post here:
A cell and gene therapy development center is taking 680K square feet at KOP's Discovery Labs - Technical.ly

Passage Bio Jim Wilsons self-described legacy company has wooed a seasoned biotech executive to steer the clinical entry of its first three gene therapy programs.

Bruce Goldsmith jumps to the helm of Passage after a brief CEO stint at Civetta, a cancer-focused startup he helped launch while a venture partner at Deerfield. He takes over from OrbiMed partner and interim chief Stephen Squinto, who will now lead the R&D team.

He joins as the biotech preps IND filings for three lead programs in rare, monogenic diseases of the central nervous system in 2020 the lysosomal storage disorders GM1 gangliasidosis and Krabbe disease, as well as frontotemporal dementia.

Bruce is ideally suited to lead Passage Bio as chief executive officer given his strong neuroscience background coupled with his robust healthcare and biotechnology industry experience, board chairman Tachi Yamada said in a statement.

Passage launched last February with $115 million from a marquee group of Series A investors including Frazier (where Yamada is a partner), OrbiMed, Versant Ventures, New Leaf Venture Partners, Vivo Capital and Lilly Asia Ventures. With an office just a 10-minute walk away from Wilsons lab at the University of Pennsylvania, the company was designed to apply the gene therapy pioneers 35-year experience into cross-correctional therapies for CNS.

According to what he calls the Jim Wilson 90/10 rule, Squinto previously told Endpoints News, AAV vectors can cover and transduce 90% of motor neuron cells but only 10% to 15% of other brain cells making it difficult to go after indications where broad transduction is needed. But it can still prove useful in disorders that result from mutations in enzymes that can be taken up by neighboring cells once secreted normally.

A close pact with Penns Gene Therapy Program and Orphan Disease Center gave Passage rights to five programs right out of the gate, with options to license seven more.

Its a very aggressive clinical development strategy across a multitude of programs, Squinto said as he closed a $110 million Series B in September. Were not gonna rely on any one program to drive the value of Passage, were gonna rely on what is a very very full pipeline of opportunities.

Goldsmith will now lead a team of about 25 to build on preclinical and IND-enabling data from Wilsons lab a company growing exercise he honed as COO of Lycera. There, he was also credited for a number of business development initiatives.

The transition into the clinic would also mean moving production from early facilities at Penn to Paragons GMP sites, and eventually to a customized suite slated for completion in the third quarter of this year.

Squinto, a rare disease expert who devoted much of his career to Alexion, will continue to help oversee all of that as a board director.

See the original post:
Eyeing a trio of trial initiations, Jim Wilson's gene therapy startup woos Bruce Goldsmith from Deerfield as CEO - Endpoints News