A pair of cancer immunotherapy developers have raised a combined nearly $150 million in Series B financings toward development of new platform technologies, treatments, and facilities.

Gritstone Oncology, which aims initially to develop tumor-specific neoantigen-targeted immunotherapies for lung and gastric cancer, said yesterday it completed a $92.7 million financing—while Replimmune Group, which focuses on developing next-generation oncolytic immunotherapies, said today it has raised $55 million.

Replimmune said today it will use proceeds from its financing primarily to generate human proof-of-concept data for lead product RP1 in multiple solid tumor types.

RP1 is a proprietary new high potency backbone virus engineered for oncolytic use, and designed to activate both innate and adaptive immune responses.

RP1 is intended to deliver optimized immune activating proteins directly into the immune response-initiating tumor and to draining lymph nodes—an approach expected to focus immune activation and potentiation on tumor antigens, and reduce the toxicity often seen with systemic antibody based approaches, according to Replummune.

Additionally, the financing will allow Replimmue to advance further product candidates from its Immulytic oncolytic immunotherapy platform, the company said.

The company’s pipeline includes RP2, an oncolytic immunotherapy designed to additionally express anti-cytotoxic T-lymphocyte-associated protein 4) (CTLA-4); and the RP3 series of oncolytic immunotherapies, designed to express anti-CTLA-4 and immune co-stimulatory ligands

‘Second Cornerstone of Immuno-Oncology’

 Replimmune says its platform is designed to maximize systemic immune activation against tumor neoantigens in conjunction with immune checkpoint blockade.: “We believe that this approach will become a second cornerstone of immuno-oncology, in addition to anti-PD1/L1,” Replimmune states on its website.

The platform is also designed to provide both maximum local tumor destruction and antigen release, as well as maximum systemic anti-tumor immune stimulation, according to Replimmune.

The company aims to apply the ability of oncolytic viruses to not only kill tumors directly, but generate an autologous vaccine to a patient’s tumor antigens directly in the patient; activate innate immunity, including through toll-like receptors (TLRs) and stimulator of interferon genes (STING); and express potent immune activating proteins including immune co-stimulatory pathway activators and antibody-like molecules targeting CTLA-4.

“These funds will also enable us to establish in house GMP manufacturing capabilities in preparation for the later stage clinical development and commercialization of our products,” Replimmune co-founder and CEO Robert Coffin, Ph.D., said in a statement.

Foresite Capital led Replimmune’s Series B financing, joined by other new investors that included Bain Capital Life Sciences, Redmile Group, Cormorant Asset Management and entities affiliated with Leerink Partners. Also “meaningfully” participating in the financing were all of the company's existing investors: Atlas Venture, Forbion Capital Partners, and Omega Funds.

Brett Zbar, M.D., a managing director with Foresite Capital, will join Replimune's board of directors, as will Kapil Dhingra, M.B.B.S., M.D., Ph.D., an advisor to the company who previously served as Roche’s head of clinical oncology.

“Securing this heavily oversubscribed financing from leading life science and biotechnology investors is a significant milestone that puts Replimune in a strong financial position.”

In its financing announcement, Replimmune also disclosed that it has appointed Howard Kaufman, M.D., FACS, as CMO.

Identifying Tumor Antigens

Gritsone Oncology yesterday said it will use proceeds from its $92.7 million preferred-stock financing to advance its tumor antigen identification platform and pipeline of personalized cancer immunotherapies.

That pipeline’s lead program—a personalized neoantigen immunotherapy in combination with checkpoint inhibitors targeting tumor-specific neoantigens—is expected to enter clinical trials in mid-2018, to be assessed initially in patients with non-small cell lung cancer and gastric cancer, Gritstone said.

Gritstone’s immunotherapy approach aims to identify and deploy neoantigens from individual patients’ tumors. The company’s proprietary technology platform is designed to identify neoantigens within the broad landscape of gene mutations using a deep learning prediction model trained on a large database of human tumors presenting peptides on the tumor cell surface.

Gritstone says it uses its model and next-generation sequencing (NGS) to characterize the tumor at a molecular level, then select neoantigens for generating a tumor- and patient-specific immunotherapy. The neoantigens are sent to Gritstone’s manufacturing facility for synthesis into a personalized neoantigen “cassette” that is part of the immunotherapy.

After viral and RNA-based vectors are generated, Gritstone adds, they are formulated, packaged in vials, and sent to physicians, where they can be administered via injection to patients to generate tumor-specific T-cell responses against the neoantigen, with the goal of destroying the tumor. 

“Since the formation of the company two years ago, Gritstone has made significant progress leveraging extensive human tumor molecular analysis and machine learning to develop and optimize the proprietary Gritstone EDGE tumor antigen identification platform,” Andrew Allen, M.D., Ph.D., Gritstone Oncology’s co-founder, president and CEO.

Gritstone also said its financing will also support ongoing construction and completion of its 43,000-square-foot industrialized manufacturing facility in Pleasanton, CA. The cGMP facility will anchor Gritstone’s manufacturing program for personalized cancer therapeutics, with the first investigational products for clinical research expected to be manufactured there in 2018.

Lilly Asia Ventures led Gritstone’s financing round, with participation from GV (formerly Google Ventures), Trinitas Capital (Beijing), and Alexandria Venture Investments, all new investors. All existing investors are also all participating in the round, including Versant Ventures, The Column Group, Clarus Funds and Frazier Healthcare Partners.

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