Introduction
Sangamo Therapeutics (SGMO) is a clinical-stage biotech company focusing on the research and development of genomic medicine across 4 distinct technology platforms: gene therapy, cell therapy, in vivo genome editing, and in vivo genome regulation.
Sangamo is best-known for developing its proprietary gene-editing technology, zinc finger proteins ("ZFPs"), which is a naturally occurring class of transcription factor proteins found in humans and other species. The company has used its internal know-how and technical expertise to develop a proprietary synthetic ZFP platform with potential clinical utility in ex vivo gene-edited cell therapy, in vivo genome editing, and in vivo genome regulation.
ZFPs also can be engineered to make zinc finger nucleases ("ZFNs") which proteins that can be used to specifically modify DNA sequences by knocking in or knocking out select genes, or genome editing, and ZFP transcription-factors ("ZFP-TFs") which are proteins that can be used to selectively increase or decrease gene expression.
Sangamo is developing a series of clinical programs, which are either wholly-owned or partnered with well-established pharma and biotech companies, to focus on 3 therapeutics areas in inherited metabolic disease ("IMDs"), central nervous system ("CNS), and inflammatory and autoimmune diseases. Its full list of clinical pipeline programs is listed in Figure 1.
Figure 1 Sangamo Therapeutics' Clinical Pipeline (Source)
The company's most advanced program is an investigational gene therapy for severe hemophilia A, SB-525. SB-525 is developed under a global collaboration with Pfizer (PFE), of which the rights of SB-525 have been transferred to Pfizer to run a phase 3 trial. In December 2019, both companies announced updated initial data from the phase1/2 trial of SB-525. SB-525 was generally well-tolerated and demonstrated a sustained increase in Factor VIII activity. SB-525 has been granted RMAT, Orphan Drug, and Fast Track designation by the FDA as well as Orphan Medicinal Product Designation by the European Medicines Agency ("EMA").
Beyond SB-525, the company is also investigating 2 wholly-owned gene therapy. ST-920 is being evaluated to treat Fabry disease, a rare inherited metabolic disease, in a phase 1 study in the US and UK. SB-920 has received Orphan Drug designation by the FDA. The company also plans to advance ST-101 into clinical trials in 2021 to treat phenylketonuria ("PKU") which is a rare inherited disorder that originates from a defect in the PAH gene and results in a harmful accumulation of phenylalanine in cells throughout the body.
Sangamo is working with Sanofi (NASDAQ:SNY) to develop ex vivo gene-edited cell therapies, ST-400 and BIVV-003, for transfusion-dependent beta-thalassemia ("TDT") and sickle cell disease ("SCD") respectively. Both ST-400 and BIVV-003 are related product candidates using the same technology involving gene editing of a patient's own hematopoietic stem progenitor cells using non-viral delivery of ZFN technology.
Sangamo is the phase 1/2 study of ST-400 in 6 patients with TDT while Sanofi is recruiting the phase1/2 study evaluating BIVV-003 in patients with SCD, and Sanofi is responsible for the subsequent development, manufacturing, and commercialization of both programs.
In Dec 2009, Sangamo presented interim results for the first 3 patients ST-400. As of the data cut date, 2 more patients have been enrolled although they were not included in the interim updates. The 3 patients treated with ST-400 experienced prompt hematopoietic reconstitution, demonstrating neutrophil engraftment in 14-22 days and platelet engraftment in 22-35 days. No emerging clonal hematopoiesis had been observed as measured by on-target indel pattern monitoring in the three treated patients. The downside of the data readout is that its treatment of TDT appears to be not as efficacious as other competitors such as bluebird bio (BLUE).
Sangamo also has a global collaboration and license agreement with Kite Pharma, a wholly-owned subsidiary of Gilead Sciences (GILD), for the development of engineered cell therapies for cancer. The company is working together with Kite to design ZFNs and viral vectors to disrupt and insert select genes in T cells and natural killer cells. The first program of this agreement expected to start a clinical trial in 2020 is KITE-307, which is an allogeneic anti-CD19 CAR-T cell therapy. Given the well-documented struggles of Kite's approved autologous CAR-T, Yescarta, the success of allogeneic CAR-Ts will be very beneficial.
Lastly, Sangamo is also evaluating the potential of regulatory T-cells ("Tregs") genetically modified with a CAR ("CAR-Tregs") in solid organ transplantation. CAR-Treg cell therapies are being conducted in several preclinical studies in autoimmune and inflammatory diseases such as multiple sclerosis ("MS") and inflammatory bowel disease ("IBD"). The most advanced CAR-Treg cell therapy is TX200, which is an autologous treatment for the prevention of solid organ transplant rejection and the clinical trial is expected to be initiated in 2020.
Sangamo is only planning to start a new clinical trial for its in vivo genome editing programs. SB-913 is a second-generation ZFNs program that will be used to treat Mucopolysaccharidosis type II ("MPS II") and a new clinical trial is planned to start this year.
The company had previous programs from first-generation ZFNs that have been halted as they did not demonstrate enough clinical benefits. The company plans to use data from the SB-913 study to definite the next steps for its in vivo genome editing programs.
The company also has several preclinical programs evaluating their ZFP-TF technology as a novel therapeutic approach for CNS diseases. In December, Sangamo announced a collaboration with Biogen (BIIB) to develop and commercialize ST-501 for tauopathies including Alzheimer's disease, ST-502 for synucleinopathies including Parkinson's disease, a third undisclosed neuromuscular disease target, and up to 9 additional neurological disease targets. Under the terms of the agreement, Biogen will pay Sangamo $350M upfront, inclusive of a license fee and equity investment, and Sangamo is eligible to receive up to $2.37B in future milestones.
Sangamo also has a partnership with Pfizer and Takeda (NYSE:TAK) to develop and evaluate ZFP-TFs. The company is working with Pfizer to evaluate ALS and frontotemporal lobar degeneration ("FTLD") that are linked to the mutations in the C9ORF72 gene. In the partnership with Takeda, the company is evaluating a preclinical program for Huntington's disease in which ZFP-TF is designed to differentially down-regulate the mutated disease-causing huntingtin gene ("HTT gene") while preserving the expression of the normal version of the gene.
As of 31 December, 2019, cash and equivalents on hand was $385M. The amount is excluding the $350M injection from the collaboration with Biogen, and when factored in, cash on hand should comfortably be in the range of high $600-700M. This should give them a comfortable runway to fund all operations well into 2021, an important point given that the recent stock market crash which limits any secondary offering options.
Impressively, the company has managed to strike several high-profile partnerships with 5 global biotech/big pharma companies. Such partnerships not only validate Sangamo's technology and capabilities, but they also provide future avenues of funding with as much as $6.34B royalties on net product sales and potential milestone payments due to the company.
Figure 1 Sangamo Therapeutics' Partnerships (Source)
In terms of competition, the company competes with several players, particularly in the cell and gene therapy space. bluebird bio has more advanced programs in both TDT and SCD and, to date, has shown much better efficacy. There are also other companies such as CRISPR Therapeutics (CRSP) that are using an alternative gene-editing method, CRISPR/Cas9 in gene therapy. Other companies such as Editas Medicine (EDIT) and Intellia Therapeutics (NTLA) are also developing CRISPR/Cas9 for treatments in TDT and SCD, although it must be noted that these are not their lead programs.
In terms of allogeneic CAR-T, there are more established players such as Allogene Therapeutics (ALLO), Cellectis (CLLS), and Precision Biosciences (DTIL). The main difference among these companies is primarily the choice of gene-editing tools with Allogene and Cellectis using TALEN while Precision is using ARCUS. All these companies are, currently, in a similar stage of clinical development.
In addition to healthy donors derived allogeneic therapies, Fate Therapeutics (FATE) is developing allogeneic therapies from induced pluripotent stem cells ("iPSCs") as a renewable cell source. The advantage of this is that product consistency and potency will be improved, and the manufacturing process will be akin to the well-established biologics where they are produced from a single cell line. It is notable to note that Allogene is also investigating using iPSCs as a renewable cell source. Also, Atara Biotherapeutics (ATRA) is developing an Epstein-Barr Virus ("EBV")-based allogeneic T cell therapy platform. Their lead program is in Phase 3 and a BLA filing is expected by the second half of the year. That should put them in the lead position of commercializing an allogeneic T cell therapy and the company is gradually moving into allogeneic CAR-T space as well.
Sangamo is, currently, trading at a market cap of around $700M, which is almost as much as its cash position. While its cash position will eventually deplete to fund operations and clinical trials, the current valuation means that there is also no value for its technology and intellectual position. I consider it a good time to take up a small position in Sangamo, especially if investors have a time horizon of at least a year to weather the COVID-19 black swan event and wait for further clinical updates from the company.
It must be cautioned though that investing in clinical-stage biotech can be extremely risky, given the binary nature of the field. This is especially so, given the market turmoil from the COVID-19 pandemic. The pandemic has also led to several countries announcing lockdowns, which have disrupted supply chain and operations. Several clinical trials have already been delayed globally and this may impact Sangamo negatively, as their cash burn will continue even if clinical trials are delayed.
Disclosure: I am/we are long ATRA, BLUE. I wrote this article myself, and it expresses my own opinions. I am not receiving compensation for it (other than from Seeking Alpha). I have no business relationship with any company whose stock is mentioned in this article.
Read the rest here:
Sangamo Therapeutics: Market Cap Is At A Bargain Relative To Its Cash Position - Seeking Alpha
- Stem Cell Therapy for Kidney Failure [Last Updated On: April 1st, 2011] [Originally Added On: April 1st, 2011]
- Dogged by pain -- stem cell therapy for dogs [Last Updated On: June 24th, 2013] [Originally Added On: April 3rd, 2011]
- Dogs now getting stem cell therapy [Last Updated On: April 8th, 2011] [Originally Added On: April 8th, 2011]
- Stem Cells for Spinal Cord Injury: Community Outreach San Diego 2011 - Trish Stressman [Last Updated On: April 11th, 2011] [Originally Added On: April 11th, 2011]
- Stem Cell Treatment Doing Wonders For Autistic Boy [Last Updated On: April 14th, 2011] [Originally Added On: April 14th, 2011]
- Is Stem Cell Therapy right for your pet [Last Updated On: April 14th, 2011] [Originally Added On: April 14th, 2011]
- Regenerative Medicines [Last Updated On: May 19th, 2011] [Originally Added On: May 19th, 2011]
- Stem Cell Therapy for Multiple Sclerosis [Last Updated On: June 24th, 2013] [Originally Added On: May 20th, 2011]
- Adult Stem Cell Therapy for Multiple Sclerosis [Last Updated On: May 23rd, 2011] [Originally Added On: May 23rd, 2011]
- Heart Failure Patient After Adult Stem Cell Therapy [Last Updated On: June 24th, 2013] [Originally Added On: May 30th, 2011]
- Stem Cell Therapy For Alzheimer's/Dementia [Last Updated On: June 24th, 2013] [Originally Added On: June 2nd, 2011]
- Stem Cell Therapy For Alzheimer's/Dementia [Last Updated On: June 7th, 2011] [Originally Added On: June 7th, 2011]
- Stem Cell Therapy Injections [Last Updated On: June 24th, 2013] [Originally Added On: June 8th, 2011]
- Clinical Advances in Adult Stem Cell Therapy: Dr. Jorge Paz [Last Updated On: June 24th, 2013] [Originally Added On: June 11th, 2011]
- Stem Cell Therapy MS: Sam Harrell and The Superbowl [Last Updated On: June 12th, 2011] [Originally Added On: June 12th, 2011]
- Stem Cell Therapy MS: Sam Harrell and The Superbowl [Last Updated On: June 24th, 2013] [Originally Added On: June 14th, 2011]
- Lou Gehrig's Disease (ALS): UCSD Team's Stem Cell Therapy Rationale [Last Updated On: June 14th, 2011] [Originally Added On: June 14th, 2011]
- Stem Cell Injection Treatment - Stem Cell Therapy [Last Updated On: June 18th, 2011] [Originally Added On: June 18th, 2011]
- edivet America Dog Arthritis Stem Cell Therapy Stem Cell Therapy for Equine 1 [Last Updated On: June 24th, 2013] [Originally Added On: June 23rd, 2011]
- Lou Gehrig's Disease (ALS): UCSD Team's Stem Cell Therapy Approach [Last Updated On: June 25th, 2011] [Originally Added On: June 25th, 2011]
- Adult Stem Cell Therapy Clinical Advances - Dr. Jorge Paz in San Diego, CA March 2011 [Last Updated On: July 3rd, 2011] [Originally Added On: July 3rd, 2011]
- Adult Stem Cell Therapy Clinical Advances - Dr. Jorge Paz in San Diego, CA March 2011 [Last Updated On: June 24th, 2013] [Originally Added On: July 15th, 2011]
- Duffy Gets Stem Cell Therapy [Last Updated On: June 24th, 2013] [Originally Added On: July 15th, 2011]
- WAVE3 News Adipose Stem Cell Therapy [Last Updated On: June 24th, 2013] [Originally Added On: July 16th, 2011]
- Lou Gehrig's Disease (ALS): UCSD Team's Stem Cell Therapy Approach [Last Updated On: June 24th, 2013] [Originally Added On: July 16th, 2011]
- Clinical Advances in Adult Stem Cell Therapy - Dr. Jorge Paz Rodriguez (Miami) [Last Updated On: June 24th, 2013] [Originally Added On: July 21st, 2011]
- Stem Cell Therapy for Cerebral Palsy - Holly Catalano [Last Updated On: June 24th, 2013] [Originally Added On: August 2nd, 2011]
- Bone Marrow Aspiration - Stem Cell Therapy [Last Updated On: August 5th, 2011] [Originally Added On: August 5th, 2011]
- Dr. Chein discusses Autologous Stem Cell Therapy - Palm Springs [Last Updated On: June 24th, 2013] [Originally Added On: August 12th, 2011]
- Stroke Victim Improved With Stem Cell Therapy. More at http://www.stemcellfusion.com [Last Updated On: June 24th, 2013] [Originally Added On: August 14th, 2011]
- Dr. Craig Saunders Adult Stem Cell Therapy [Last Updated On: August 15th, 2011] [Originally Added On: August 15th, 2011]
- Embryonic stem cell therapy in China (www.esctherapy.com) [Last Updated On: June 24th, 2013] [Originally Added On: August 16th, 2011]
- Ying Liu discusses IPS cell therapy for ALS [Last Updated On: June 24th, 2013] [Originally Added On: August 16th, 2011]
- Stem Cell Therapy: Healing Force of the future [Last Updated On: September 19th, 2011] [Originally Added On: September 19th, 2011]
- Benefits of STEM CELL THERAPY - Adipose Tissue [Last Updated On: September 22nd, 2011] [Originally Added On: September 22nd, 2011]
- Stem Cell Therapy Skin Repair and Anti-Wrinkle Cream [Last Updated On: June 24th, 2013] [Originally Added On: September 24th, 2011]
- Cardiac Stem Cell Therapy [Last Updated On: June 24th, 2013] [Originally Added On: September 24th, 2011]
- Holly Huber on Recovery: Stem Cell Therapy for Multiple Sclerosis Community Outreach Dallas, TX 2011 [Last Updated On: June 24th, 2013] [Originally Added On: September 24th, 2011]
- Stroke Victim Improved With Stem Cell Therapy. More at http://www.stemcellfusion.com [Last Updated On: September 25th, 2011] [Originally Added On: September 25th, 2011]
- A Touch of Love® - Stem Cell Therapy for Pets-Dr. Danny DeRose-Part 3 [Last Updated On: September 27th, 2011] [Originally Added On: September 27th, 2011]
- Adult Stem Cell Therapy for Multiple Sclerosis [Last Updated On: June 24th, 2013] [Originally Added On: September 28th, 2011]
- Multiple Sclerosis Stem Cell Therapy News Coverage [Last Updated On: June 24th, 2013] [Originally Added On: October 1st, 2011]
- The Spinal Cord Journey - Stem cell therapy stories from three spinal cord injury patients [Last Updated On: October 6th, 2011] [Originally Added On: October 6th, 2011]
- Peyton Manning Stem Cell Therapy: Some Doctors Cry Foul Over European Treatment - Video [Last Updated On: October 13th, 2011] [Originally Added On: October 13th, 2011]
- Stem-Cell-Therapy-in-China.wmv - Video [Last Updated On: October 13th, 2011] [Originally Added On: October 13th, 2011]
- Randolph veterinarian uses new stem cell therapy on ailing pets - Video [Last Updated On: June 24th, 2013] [Originally Added On: October 13th, 2011]
- Stem Cell Therapy for Rheumatoid Arthritis - Video [Last Updated On: June 24th, 2013] [Originally Added On: October 14th, 2011]
- Holly Huber on Recovery: Stem Cell Therapy for Multiple Sclerosis Community Outreach Dallas, TX 2011 - Video [Last Updated On: October 14th, 2011] [Originally Added On: October 14th, 2011]
- Affordable Stem Cell Therapy in Guatemala (2hrs from Miami) - Video [Last Updated On: June 24th, 2013] [Originally Added On: October 15th, 2011]
- Stem Cell Research: Macular Degeneration - Video [Last Updated On: October 18th, 2011] [Originally Added On: October 18th, 2011]
- Duffy Gets Stem Cell Therapy - Video [Last Updated On: October 18th, 2011] [Originally Added On: October 18th, 2011]
- VetCell's StemRegen - the original and best stem cell therapy for equine tendon injuries - Video [Last Updated On: October 20th, 2011] [Originally Added On: October 20th, 2011]
- Macular degeneration - Stem Cell therapy (English subtitles) - Video [Last Updated On: October 20th, 2011] [Originally Added On: October 20th, 2011]
- Stem Cell Therapy for Rheumatoid Arthritis - Community Outreach Dallas - Darnell Morris - Video [Last Updated On: June 24th, 2013] [Originally Added On: October 21st, 2011]
- Adult Stem Cell Therapy for Congestive Heart Failure [Last Updated On: June 24th, 2013] [Originally Added On: October 21st, 2011]
- Stem Cell Therapy for Critical Limb Ischemia: First Choice or Last Ditch? - Video [Last Updated On: October 22nd, 2011] [Originally Added On: October 22nd, 2011]
- WAVE3News Adipose Stem Cell Therapy - Video [Last Updated On: October 22nd, 2011] [Originally Added On: October 22nd, 2011]
- Stem Cell Therapy in Cardiac Disease - Video [Last Updated On: June 24th, 2013] [Originally Added On: October 24th, 2011]
- Stem Cell Treatment for Autism: Community Outreach Miami, Florida - May 2011 - Video [Last Updated On: June 24th, 2013] [Originally Added On: October 24th, 2011]
- Pre Post n 6 Months Post Stem Cell Therapy of Dystonic Cerebral Palsy - Video [Last Updated On: June 24th, 2013] [Originally Added On: October 24th, 2011]
- Stem Cell Treatment for Rheumatoid Arthritis - "I am basically pain free." - Video [Last Updated On: October 26th, 2011] [Originally Added On: October 26th, 2011]
- UMBILICAL CORD STEM CELL THERAPY - Video [Last Updated On: June 24th, 2013] [Originally Added On: October 26th, 2011]
- Stem Cell Therapy for Peripheral Artery Disease - Video [Last Updated On: June 24th, 2013] [Originally Added On: October 26th, 2011]
- Multiple Sclerosis Adult Stem Cell Therapy - Video [Last Updated On: June 24th, 2013] [Originally Added On: October 26th, 2011]
- Stem Cell Therapy for Multiple Sclerosis Stimulates IDO - Video [Last Updated On: June 24th, 2013] [Originally Added On: October 26th, 2011]
- HIV/AIDS: Spotlight on Stem Cell Research - John Zaia - Video [Last Updated On: October 26th, 2011] [Originally Added On: October 26th, 2011]
- Stem cell treatment by Adiva Health Care India after Spinal Cord Injury - Video [Last Updated On: October 27th, 2011] [Originally Added On: October 27th, 2011]
- Stem Cell Treatment for Spinal Cord Injury - Video [Last Updated On: October 28th, 2011] [Originally Added On: October 28th, 2011]
- Lou Gehrig's Disease: Stem Cell Therapy Pre-Clinical Studies - Video [Last Updated On: October 28th, 2011] [Originally Added On: October 28th, 2011]
- Stem Cell Treatment for Spinal Cord Injury - Video [Last Updated On: June 24th, 2013] [Originally Added On: October 28th, 2011]
- Holly Huber on Recovery: Stem Cell Therapy for Multiple Sclerosis Community Outreach San Diego CA - Video [Last Updated On: June 24th, 2013] [Originally Added On: October 28th, 2011]
- Stem Cell Treatment for Rheumatoid Arthritis - "I got my life back" - Video [Last Updated On: October 28th, 2011] [Originally Added On: October 28th, 2011]
- Adult Stem Cell Therapy Following Heart Attack and Stroke - Video [Last Updated On: October 28th, 2011] [Originally Added On: October 28th, 2011]
- Stem Cells - Treatment for Autism - Video [Last Updated On: November 2nd, 2011] [Originally Added On: November 2nd, 2011]
- Stem Cell Treatment Diabetes - Video [Last Updated On: November 7th, 2011] [Originally Added On: November 7th, 2011]
- Stem Cell Therapy: Psoriatic Arthritis Treatment - Video [Last Updated On: June 24th, 2013] [Originally Added On: November 8th, 2011]
- Stem Cell Therapy Cure Hair Loss. More at http://www.stemcellfusion.com - Video [Last Updated On: June 24th, 2013] [Originally Added On: November 10th, 2011]
- BioLogic Stem Cell Therapy - Video [Last Updated On: November 16th, 2011] [Originally Added On: November 16th, 2011]
- BioLogic Stem Cell Therapy - Video [Last Updated On: June 24th, 2013] [Originally Added On: November 16th, 2011]
- AVS Stem Cell Therapy - Video [Last Updated On: June 24th, 2013] [Originally Added On: November 17th, 2011]