REGENXBIO Looks to Take CLN2 Gene Therapy Treatment Into the Clinic

Maryland-based REGENXBIO is expanding its gene therapy pipeline to include a new treatment for late-infantile neuronal ceroid lipofuscinosis type 2 (CLN2) disease, one of the most common forms of Batten disease.

In an announcement this morning, REGENXBIO said the new product candidate, RGX-181, is based on the company’s proprietary NAV Technology Platform. CLN2 is a form of Batten disease caused by mutations in the tripeptidyl peptidase 1 (TPP1) gene. RGX-181 will use the company’s NAV AAV9 vector to deliver the targeted TPP1 gene to patients. The administered gene is sent to the central nervous system to induce sustained levels of TPP1, the company said in a statement. Preclinical animal models have shown a single treatment with RGX-181 resulted in “widespread distribution and sustained expression of the TPP1 enzyme in the CNS with significant improvements in neurobehavioral function and survival of the animals.”

REGENXBIO will submit an investigational new drug (IND) application for RGX-181 to the U.S. Food and Drug Administration (FDA) in 2019 in hopes of beginning global first-in-human clinical trial with clinical centers planned in the United States and Europe. REGENXBIO has two other CNS products, RGX-111 and RGX-121, in clinical trials for the treatment of Mucopolysaccharidosis Type I (MPS I) and Mucopolysaccharidosis Type II (MPS II) diseases, respectively.

Olivier Danos, chief scientific officer of REGENXBIO, said the company’s NAV platform holds “tremendous promise for advancing this new product candidate in our neurodegenerative disease pipeline.” Danos noted that CLN2 is a fatal disease is rapidly progressing with no cure. Current treatment options for CLN2 include palliative care or enzyme replacement therapy, where recombinant TPP1 is administered into the lateral ventricles via a permanently implanted device on a biweekly basis, the company noted.

“Children with CLN2 disease experience an array of serious symptoms such as seizures, deterioration of language and motor skills, blindness, cognitive decline and premature death. The goal of our RGX-181 clinical program is to develop a single-dose treatment to halt progression of neurological decline and improve a broad range of these devastating symptoms experienced by children with CLN2 disease,” Danos said in a statement.

Kenneth Mills, president and chief executive officer of REGENXBIO, said because of the unmet need and with the potential for NAV gene therapy, the company believes CLN2 is a “natural addition” to its neurodegenerative disease pipeline.

“As we prepare to initiate dosing in our clinical trials of RGX-111 for MPS I and RGX-121 for MPS II, adding RGX-181 to our research pipeline furthers our commitment to finding potential cures for children affected by these extremely serious and life-threatening neurodegenerative conditions,” Mills said.

Earlier this year, Mills told BioSpace that in 2018 the company will have one of the most diverse pipelines of gene therapy. In addition to the gene therapies the company has in its own pipeline, REGENXBIO is also working with a number of partnerships. REGENXBIO has partnerships with Audentes, Shire and Ultragenyx. In June the company saw a $100 million payday due to its expanded relationship with AveXis, now a Novartis company, to develop treatments for spinal muscular atrophy (SMA). In January the two companies amended the 2014 license agreement for REGENXBIO’s gene therapy technology.

https://www.biospace.com/article/-cp8r-regenxbio-looks-to-take-cln2-gene-therapy-treatment-into-the-clinic-/

Awash in Funding, Sutro Biopharma Files for $75 Million IPO

Only a month after raising $85.4 million in a Series E financing, Sutro Biopharma filed for an initial public offering (IPO). The company plans to raise $75 million with the IPO.

The company had a wholly-owned pipeline of cancer therapeutics, which includes two internally-developed antibody drug conjugates (ADCs). They are STRO-001, which is in Phase I clinical testing for lymphoma and multiple myeloma, and STRO-002, which is expected to enter the clinic in early 2019 for ovarian and endometrial cancer. The drugs were developed with the company’s proprietary cell-free protein synthesis and site-specific conjugation platforms. These platforms allow for precise design and rapid optimization of protein conjugates.

Sutro’s chief scientific officer, Trevor Hallam, at the time of the Series E financing, stated, “With XpressCF+, we incorporate non-natural amino acids into specific positions on the generated antibody for site-specific conjugation of cytotoxins with a linker and warhead to enable consistent, stable, pinpoint placement of STRO-001’s toxic payload. This leads to highly efficient delivery of the cytotoxin to tumor cells. By contrast, earlier generations of ADCs can have unpredictable pharmacologic properties, resulting in the potential for sub-optimal stability, compromised efficacy and poor tolerability for patients.”

The Series E was led by Samsara BioCapital and Surveyor Capital (a Citadel company). It was supported by current investors, Alta Partners, Amgen Ventures, Celgene Corporation, Lilly Ventures, Skyline Ventures and SV Health Investors. It also included first-time investors Eventide, Nexthera Capital, Vida Ventures and funds managed by Tekla Capital Management. And if the heavy-hitters of Amgen, Celgene, and Eli Lily weren’t enough, Merck also invested and committed to a future investment.

With the Series E round, the company has raised more than $175 million since it was founded in 2003.

Sutro filed with the U.S. Securities and Exchange Commission (SEC) on June 1, 2018. It plans to list on the Nasdaq under the symbol STRO. Cowen and Piper Jaffray are the joint bookrunners. No mention of IPO list price has been released.

On July 24, Sutro inked a collaboration and license deal with Merck to discover and develop novel immune-modulating therapies for cancer and autoimmune disorders. It will utilize Sutro’s the platforms. Sutro will be responsible for preclinical research and Merck will pick up exclusive worldwide rights to candidates that come from the collaboration. Merck paid Sutro $60 million upfront with potential milestone “bio-bucks” payments of up to $1.6 billion.

“Sutro has an impressive suite of technologies that make possible the discovery, characterization and manufacture of novel therapeutic proteins in a timely manner,” said Joe Miletich, senior vice president, Discovery, Preclinical and Early Development, Merck Research Laboratories, in a statement. “We look forward to collaborating with Sutro to further expand our pipeline of promising candidates targeting oncology and autoimmune diseases.”

And on August 13, Sutro partnered with The Leukemia & Lymphoma Society to develop STRO-001. The LLS is contributing undisclosed funds to Sutro through its Therapy Acceleration Program. Sutro plans to use the funds for a Phase I trial that began in April 2018 and is enrolling at City of Hope Comprehensive Cancer Center in Duarte, California, Medical College of Wisconsin in Milwaukee, Texas Oncology in Austin, Rocky Mountain Cancer Centers in Aurora, Colorado, and Virginia Cancer Specialists in Fairfax. It appears to be almost a loan arrangement because Sutro is required to make payments to LLS on pre-specified late-stage clinical development, regulatory and commercialization milestones.

“LLS is committed to advancing therapies to address critical unmet need,” said Lee Greenberger, LLS’s chief scientific officer, in a statement. “New options for therapies are vital for patients with non-Hodgkin’s lymphoma and myeloma who do not respond to available treatments. Sutro’s approach offers a promising option for these patients.”

https://www.biospace.com/article/-ip3o-awash-in-funding-sutro-biopharma-files-for-75-million-ipo/

Vertex, Machine Learning Company Genomics Plc Enter 3-Year Collaboration

Cystic fibrosis drugmaker Vertex Pharmaceuticals forged a three-year collaborative dealwith U.K.-based machine learning specialist Genomics plc to improve the discovery of targets for precision medicines.

The companies will harness Genomics machine-learning technology to gain a greater understanding of the “clinical impact of human genetic variation and patient stratification in diseases with significant unmet need.” Boston-based Vertex said the partnership, which could be expanded to five years, will further advance the company’s efforts to develop transformative precision medicines for people with serious diseases.

U.K.-based Genomics plc’s analysis engine used genetics to understand human biology and the likely efficacy and safety of potential novel medicines, according to company data. The Genomics engine includes more than 100 billion data points and links “human genetic variation at over 14 million positions in the human genome to changes in 7,000 molecular, cellular, and physiological measurements and disease outcomes.” Through the use of proprietary machine learning and statistical algorithms, Genomics can predict the impact of therapeutic interventions, the company said.

Researchers from Vertex and Genomics will collaborate on targeting certain diseases, although they did not disclose which diseases would be in their sights for this project. The companies noted the diseases will be ones where “human genetic evidence may be particularly powerful.”

Genomics founder and chief executive officer Peter Donnelly said genetics has been shown to have a “substantial impact” on novel drug targets. Genomics next generation of data and algorithms “promises to be transformative, not just for target discovery but in biomarker selection and patient stratification,” he said. Donnelly added that the partnership with Vertex will allow Genomics to realize such a promise to benefit patients and their families.

In an interview with The Telegraph of London, Donnelly said that about 90 percent of drugs taken into the clinic fail. That’s largely due to a lack of understanding about human biology. That’s where the machine learning Genomics provides can help in the process, he said. In his interview with The Telegraph, Donnelly explained how Genomics can help drug manufacturing companies.

“If you are drug company and want to stop a disease by inhibiting say, a protein, we can use our technology to look for individuals who have a genetic variance that inhibits that same protein, a natural weak version of the drug if you like, and see what happens to them and say, if you inhibit that protein, these things will happen to them,” he told The Telegraph.

David Altshuler, head of global research and chief scientific officer of Vertex, said the partnership with Genomics plc will “pioneer new uses of genomic tools and technologies” that will advance the research Vertex is doing.

Under terms of the deal, Vertex will make undisclosed milestone and royalty payments to the company for novel targets resulting from the collaboration that are taken through clinical development. Altshuler will also join the Genomics plc Board of Directors.

In addition to the collaboration, Vertex also invested $13.6 million into a Series B financing round for Genomics plc.

https://www.biospace.com/article/vertex-and-machine-learning-company-genomics-plc-enter-three-year-collaboration-am6a-/

Exact Sciences price target raised to $75 from $45 at Goldman Sachs

Goldman Sachs analyst Patrick Donnelly raised his price target on Exact Sciences (EXAS) to $75, citing the positive impact of its co-promotion agreement with Pfizer (PFE) on Cologuard announced last week. The analyst expects the transaction to be “fundamentally transformative” for Exact Sciences over the next 3-4 years in terms of its revenue growth potential, but sees the 50% upside reaction in the stock price as sufficient in capturing the upside. Donnelly keeps his Neutral rating on Exact Sciences.

https://thefly.com/landingPageNews.php?id=2783925

Pfizer terminates domagrozumab clinical studies for the treatment of Duchenne

Pfizer announced that it is terminating two ongoing clinical studies evaluating domagrozumab for the treatment of Duchenne muscular dystrophy: a Phase 2 safety and efficacy study and an open-label extension study. The Phase 2 study, did not meet its primary efficacy endpoint, which was to demonstrate a difference in the mean change from baseline in 4 Stair Climb following one year of treatment with domagrozumab as compared to placebo in patients with DMD. Further evaluation of the totality of evidence including secondary endpoints did not support a significant treatment effect. The decision comes after a thorough review of data available at the time of the primary analysis, which evaluated all study participants after one year of treatment, as well as those participants who were in the trial beyond one year. The studies were not terminated for safety reasons. Pfizer will continue to review the data to better understand any insights they may provide, and will share results with the scientific and patient community. Pfizer is continuing research in DMD and rare neuromuscular diseases, with the goal of bringing therapies to patients with unmet needs. The company’s continued partnership with advocacy associations and the community is critical to finding innovative therapies for these diseases. Pfizer has one ongoing clinical trial in DMD with a gene therapy, PF-06939926, which is an investigational, recombinant AAV9 capsid carrying a truncated or shortened version of the human dystrophin gene under the control of a human muscle specific promotor. The Phase 2 double-blind, placebo-controlled, multicenter clinical trial investigated the efficacy and safety of domagrozumab, administered in monthly IV doses, in 121 boys aged 6 to 15 with DMD, regardless of underlying mutation. It was designed as a two-year, placebo-controlled study; all subjects used background corticosteroid therapy. The open-label extension study was designed to evaluate long-term safety and efficacy of domagrozumab.
https://thefly.com/landingPageNews.php?id=2783945

Stryker acquires K2M Group for $1.4B

K2M Group (KTWO) announced a definitive merger agreement with Stryker (SYK) pursuant to which Stryker has agreed to acquire all of the issued and outstanding shares of common stock of K2M in an all cash transaction for $27.50 per share, or a total equity value of approximately $1.4B. The purchase price represents a 27% premium over K2M’s average closing price during the 90 trading days ended August 29. Upon completion of the proposed transaction, K2M will become a wholly owned subsidiary of Stryker. Post-closing, K2M’s Chairman, CEO, and president Eric Major is expected to be appointed as the president of Stryker’s spine division. The proposed transaction is expected to close late in Q4, subject to customary closing conditions, including approval by K2M’s stockholders and the receipt of certain regulatory approvals. The proposed transaction has been approved by the board of both companies and is not subject to any financing condition.

https://thefly.com/landingPageNews.php?id=2783959

Canopy Growth presentation thorough, but didn’t include ‘new news,’ says Stifel

Stifel analyst Christopher Growe said Canopy Growth’s (CGC) investor day presentation provided a thorough introduction to the company, but was “devoid of new news.” The Constellation (STZ) partnership dramatically increased interest in the event and he came away impressed with the level of professionalism of the organization, Growe tells investors. Canopy’s valuation has been pushed to 19X EV/Sales when considering FY20 consensus estimates and whether this accurately captures Canopy’s advantaged position is “open for debate,” added Growe.

https://thefly.com/landingPageNews.php?id=2784081