On January 13, 2021 Jounce Therapeutics, Inc. (NASDAQ: JNCE), a clinical-stage company focused on the discovery and development of novel cancer immunotherapies and predictive biomarkers, reported the initiation of patient enrollment in the INNATE Phase 1 clinical study of its lead macrophage program JTX-8064 as a monotherapy and in combination with either JTX-4014, its internal PD-1 inhibitor, or pembrolizumab in patients with advanced solid tumors (Press release, Jounce Therapeutics, JAN 13, 2021, View Source [SID1234573951]). JTX-8064, the first tumor-associated macrophage candidate developed from Jounce’s Translational Science Platform, is a humanized IgG4 monoclonal antibody designed to specifically bind to the macrophage receptor Leukocyte Immunoglobulin Like Receptor B2 (LILRB2/ILT4), inhibiting LILRB2 binding with its ligands and reprogramming immune-suppressive macrophages to enhance anti-tumor immunity.

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"We are pleased to announce we have dosed the first patient in our INNATE Phase 1 study which is designed to progress quickly through dose escalation and demonstrate proof of concept in tumor specific expansion cohorts," said Beth Trehu, M.D., chief medical officer at Jounce Therapeutics. "Expansion cohorts in INNATE will address multiple different patient populations, including PD-(L)1 inhibitor naïve patients with both PD-(L)1 inhibitor sensitive and resistant tumor types, and PD-(L)1 inhibitor experienced patients whose tumors were resistant to PD-(L)1 inhibitors. Patients with PD-(L)1 inhibitor resistant tumors represent a large and growing unmet medical need. We believe LILRB2 may function as an immune checkpoint for macrophages and JTX-8064 may have the potential to restore PD-(L)1 inhibitor activity in otherwise resistant settings. INNATE will also assess pharmacodynamic and potential predictive biomarkers to guide future development, aligning with Jounce’s philosophy of developing the right immunotherapies for the right patients."

The Phase 1 INNATE study will consist of 4 parts:

JTX-8064 monotherapy dose escalation in solid tumors
JTX-8064 dose escalation in combination with Jounce’s PD-1 inhibitor, JTX-4014, and also with pembrolizumab in solid tumors
JTX-8064 monotherapy in indication-specific expansion cohorts
JTX-8064 in combination with JTX-4014 or pembrolizumab in indication-specific expansion cohorts
ClinicalTrials.gov identifier: NCT04669899

About JTX-8064
JTX-8064 is a humanized IgG4 monoclonal antibody designed to specifically bind to Leukocyte Immunoglobulin Like Receptor B2 (LILRB2/ILT4) and block interactions with its ligands. JTX-8064 is the first tumor-associated macrophage candidate developed from Jounce’s Translational Science Platform. Preclinical data presented at the 2020 Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper)’s Annual Meeting and the 2019 American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting support the development of JTX-8064 as a novel immunotherapy to reprogram immune-suppressive macrophages and enhance anti-tumor immunity. A Phase 1 clinical study named INNATE (NCT04669899), for JTX-8064 as a monotherapy and in combination with JTX-4014 or pembrolizumab, is currently enrolling patients with advanced solid tumors.

About JTX-4014
JTX-4014 is a well-characterized fully human IgG4 monoclonal antibody designed to block binding to PD-L1 and PD-L2. JTX-4014 demonstrated a 17% durable overall response rate in a Phase 1 trial of 18 heavily pre-treated PD-(L)1 inhibitor naïve patients, which excluded all tumor types for which PD-(L)1 inhibitors were approved. In this Phase 1 trial, JTX-4014 was shown to have an acceptable safety profile. JTX-4014 is currently being assessed in the INNATE Phase 1 trial (NCT04669899) in combination with JTX-8064, a LILRB2 (ILT4) inhibitor. JTX-4014 is also being assessed in the SELECT Phase 2 clinical trial (NCT04549025) in combination with vopratelimab, a clinical-stage monoclonal antibody that binds to and activates ICOS, the Inducible T cell CO-Stimulator, a protein on the surface of certain T cells commonly found in many solid tumors. The SELECT trial compares vopratelimab plus JTX-4014 to JTX-4014 alone in immunotherapy naïve NSCLC patients who have been pre-selected with the TISvopra predictive biomarker, an 18 gene RNA tumor inflammation signature which predicted the emergence of ICOS hi CD4 T cells and clinical benefit in the ICONIC trial of vopratelimab alone and in combination with a PD-1 inhibitor.

On January 13, 2021 IO Biotech, a clinical-stage biopharmaceutical company developing novel, immune-modulating anti-cancer therapies based on its proprietary T-win technology, reported that it has raised EUR 127 million in Series B financing (Press release, IO Biotech, JAN 13, 2021, View Source [SID1234573924]). The financing round was led by HBM Healthcare Investments, and other new investors joining the round included Vivo Capital, Kurma Partners, Avoro Capital, RA Capital Management, Samsara Biocapital, Idinvest Partners1, PFM Health Sciences, Soleus Capital, Eir Ventures and Serrado Capital, with the participation of existing investors Novo Seeds, Lundbeckfonden Emerge and Sunstone Life Science Ventures. Additionally, Dr. Priyanka Belawat of HBM Partners, Jack B. Nielsen of Vivo Capital and Vanessa Malier of Kurma Partners will join IO Biotech’s board of directors as part of the closing of the financing.

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On December 15, 2020, the U.S. Food and Drug Administration (FDA) granted IO Biotech breakthrough therapy designation for a combination of the potential therapies IO102 and IO103 with anti-PD-1 monoclonal antibodies for patients with unresectable or metastatic melanoma. IO Biotech intends to use the net proceeds of the transaction towards the funding of clinical trials for its early and late-stage immuno-oncology programs, including a large randomized trial for IO102 and IO103 with anti-PD-1 monoclonal antibodies in metastatic melanoma.

"We are excited to have such a strong group of investors backing our company at this stage, and I am proud that this financing round had such high interest and can close oversubscribed," said Mai-Britt Zocca, PhD, Chief Executive Officer, and founder of IO Biotech. "The funding will enable us to execute on our breakthrough therapy designation grant and advance our lead programs in late-stage clinical development, as we are committed to bringing our treatment to patients as soon as possible."

"HBM is excited to be joining IO Biotech as a shareholder. IO Biotech offers a unique treatment modality in oncology, harnessing novel immunomodulatory mechanisms through proprietary vaccine candidates. The financing will help the company bring forward its promising clinical and pre-clinical pipeline closer to the patients in medical need," said Dr. Priyanka Belawat, Investment Advisor at HBM Partners.

"IO Biotech is building a significant immunotherapy pipeline based on compelling scientific and clinical validation. On behalf of existing investors, I warmly welcome the new investors to the company," said Christian Elling, Managing Partner at Lundbeckfonden Emerge. "Together we can accelerate the development of the company’s unique breakthrough cancer medicines to the benefit of patients and physicians."

About IO102 and IO103
IO102 and IO103 are IO Biotech’s lead immuno-oncology candidates. Both compounds are based on IO Biotech’s proprietary T-win technology platform which enables the identification of compounds with a dual mechanism of action targeting and directly killing immunosuppressive cells and tumor cells while indirectly activating other T-effectors, leading to strong anti-tumor responses without adding additional safety concern. Specifically, IO102 and IO103 are first-in-class, immune modulatory vaccines designed to engage and activate IDO and PD-L1 specific human T-cells.

The FDA decision to grant breakthrough therapy designation was based on data from the MM1636 Phase 1/2 clinical trial of 30 patients with metastatic melanoma receiving IO102, IO103 and anti-PD-1 monoclonal antibodies. According to the data recently presented in a late-breaking abstract at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Virtual Congress 2020, the combination of IO102 and IO103 vaccines and nivolumab was shown to be safe with encouraging early efficacy data; an overall response rate (ORR) of 79 percent was reached and 45 percent of patients achieved a complete response (CR), or complete disappearance of their tumors. Vaccine specific T-cells were located in the peripheral blood mononuclear cells (PBMCs) and at the tumor site.

On January 13, 2021 Taiho Pharmaceutical Co, Ltd., (hereinafter Taiho) reported that it and Astex Pharmaceuticals (UK), (hereinafter Astex), both Otsuka group companies, have granted an exclusive license under their joint, small-molecule drug discovery program targeting SHP2 to Merck & Co., Inc., Kenilworth, NJ, USA, known as MSD outside the United States and Canada (hereinafter MSD) through a subsidiary (Press release, Taiho, JAN 13, 2021, View Source [SID1234573914]).

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An option for MSD to acquire the exclusive license to the Astex-Taiho SHP2 program was included as part of the strategic oncology collaboration between MSD, Astex and Taiho, announced in January 2020. The collaboration focuses on the discovery and development of small molecule inhibitors against several drug targets, including the KRAS oncogene, which are currently being investigated for the treatment of cancer.

SHP2, a dephosphorylating enzyme, is a signaling molecule which regulates various cellular processes including cell proliferation and differentiation, and acts as a regulator in the activation of the RAS signaling pathway such as KRAS.*1

"We are delighted to have extended the breadth of our strategic oncology collaboration with MSD to encompass assets from the joint Astex-Taiho SHP2 program", said Teruhiro Utsugi, Ph.D., managing director at Taiho. "This will allow for a number of important drug-drug combinations to be explored as potential new treatment modalities for patients."

In exchange for providing MSD with an exclusive global license to their small molecule SHP2 inhibitor candidates, Taiho and Astex will receive an option-exercise fee payment and will be eligible to receive further undisclosed payments contingent upon the achievement of clinical, regulatory and sales milestones for SHP2 products, as well as tiered royalties on sales. MSD will be solely responsible for funding all further research and development and will be responsible for commercialization of SHP2 products globally. Taiho has retained co-commercialization rights in Japan and an option to promote SHP2 products in specific areas of Southeast Asia.

"We are pleased with the discovery research progress and collaboration with Taiho and Astex as we seek to develop new small molecule candidates for the treatment of cancer," said Nick Haining, vice president, Discovery Oncology and Immunology, MSD Research Laboratories. "We look forward to working more extensively with Taiho and Astex on the SHP2 pathway and accelerating this promising research which has the potential to impact a number of cancer types."

Harren Jhoti, Ph.D., president and CEO of Astex Pharmaceuticals (UK), commented,

"Together with our Taiho colleagues, we are delighted to extend our strategic alliance with MSD to include assets from our joint SHP2 program that have been generated using our leading fragment-based drug discovery approach."

On January 13, 2021 Astellas Pharma Inc. (TSE: 4503, President and CEO: Kenji Yasukawa, Ph.D., "Astellas" ) reported that it has entered into a research collaboration for molecular targeted radiotherapies with Actinium Pharmaceuticals, Inc. (NYSE AMERICAN: ATNM, Chief Executive Officer and Chairman of the Board: Sandesh Seth, "Actinium") (Press release, Astellas, JAN 13, 2021, View Source [SID1234573913]). This collaboration is a component of Astellas’ initiative to develop "theranostics" as part of its Rx+ business1.

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Theranostics is a combined term of "therapeutics" and "diagnostics", defined as a treatment protocol or concept in which healthcare professionals assess lesion sites and simultaneously determine the appropriate treatment for each patient2. Through utilization of a diagnostic agent developed in parallel with a therapeutic agent that shares the same target, it may be possible to identify patients in advance who would benefit from the treatment. This approach may help healthcare professionals provide more efficient and effective treatment.

In this collaboration, the potential therapeutic effect will be assessed by combining certain targeted oncology drugs that were discovered by Astellas based on its drug discovery capabilities cultivated thus far with Actinium’s nuclear medicine technology which utilizes an alpha particle-emitting radioisotope3 (Actinium-225). Astellas is already conducting pre-clinical trials of the diagnostic agents on the target　molecule．When a promising therapeutic drug candidate is identified in the course of this collaboration, clinical trials for the theranostics may be initiated.

Through its Rx+ business, Astellas aims to realize a society where people can live in their own way, both physically and mentally through scientifically based on scientific evidence. Astellas aims to optimize therapeutic approach by improving diagnostic and surgical accuracy and maximize patient outcomes. The development of theranostics that integrates diagnostics and therapeutics is part of this effort.

Astellas has already reflected the impact from this collaboration in its financial forecast of the current fiscal year ending March 31, 2021.

On January 12, 2021 PharmEnable reported that the company has entered a new partnership with Sosei Heptares (Press release, PharmEnable, JAN 12, 2021, View Source [SID1234641050]). This collaboration will drive a novel drug discovery programme against a challenging G protein-coupled receptor (GPCR) target, which is associated with neurological disease.

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Sosei Heptares is an international biopharmaceutical group, focused on the discovery and early development of new medicines originating from their world-leading GPCR-targeted StaR technology and structure-based drug design platform capabilities.

Miles Congreve, Chief Scientific Officer of Sosei Heptares, said: "We have been very impressed with PharmEnable’s technology and approach, which we believe to be highly complementary to our own, offering important synergies for drug discovery on challenging GPCR targets. We are excited to apply these technologies on a peptidergic GPCR target that has proved particularly difficult to drug. We have so far assembled a wealth of structural and ligand-binding information on the target and created several promising molecules but have yet to identify compounds with sufficiently desirable neurological drug-like properties to advance into preclinical studies. Combining our respective technologies and expertise may be the key that unlocks this target and enables the identification of higher quality molecules to progress into preclinical development."

Dr Hannah Sore, Founder and CEO of PharmEnable, commented: "We are excited to partner with Sosei Heptares on this challenging and complex GPCR target. We have proven the strength of our platform in tapping unexplored parts of the chemical universe to find novel and specific hits for currently undruggable targets. Combining our platform with the technology and structural insights developed by Sosei Heptares should enable us to generate several potential hits, and to establish our pipeline of candidate molecules for the treatment of challenging diseases.".

The collaboration will enhance innovation and development of the next generation of small molecule drugs against the particularly difficult GPCR target. PharmEnable is excited to begin this collaborative project and look forward to working closely with Sosei Heptares.