On September 14, 2022 Alligator Bioscience (Nasdaq Stockholm: ATORX) reported a poster presentation on the OPTIMIZE-1 Phase 1b/2 trial of mitazalimab in combination with modified FOLFIRINOX in first-line metastatic pancreatic cancer with the company’s lead asset mitazalimab (CD40 mAb) at the 2022 AACR (Free AACR Whitepaper) (American Association for Cancer Research) Special Conference on Pancreatic Cancer, being held in Boston September 13-16 (Press release, Alligator Bioscience, SEP 14, 2022, View Source [SID1234619538]).

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The presentation, entitled "Mitazalimab (CD40 agonist) in combination with mFOLFIRINOX in patients with metastatic pancreatic ductal adenocarcinoma (mPDAC); Safety data and recommended dose of phase 2 (RP2D) from OPTIMIZE-1, a phase 1b/2 study", outlines additional results from the Phase 1b dose escalation part of the study that were announced in March, 2022 (press release).

The results presented at AACR (Free AACR Whitepaper), demonstrate that mitazalimab is safe and tolerable at 900 µg/kg, the highest dose tested in OPTIMIZE-1. Most of the mitazalimab related AEs at both dose levels (fever, muscle pain, loss of apetite and fatigue) were mild to moderate (grade 1 or 2) severity and manageable. Only one patient out of the 6 patients in the 900 µg/kg cohort experienced a grade 3 treatment-related adverse event (TRAE) of headache. There were no grade 4 TRAEs or treatment related death reported. Pharmacodynamic markers in peripheral blood confirmed immune activation, in accordance with mitazalimab’s mode of action.

Overall, the data showed that mitazalimab combined with mFOLFIRINOX is safe and well tolerated. The 900 µg/kg dose of mitazalimab was selected as the recommended dose for the Phase 2 study. Enrollment for the Phase 2 is ongoing at sites in Europe with an interim efficacy and safety read-out expected in Q4 2022.

"The AACR (Free AACR Whitepaper) Special Conference on Pancreatic Cancer is an extremely well-regarded scientific forum for Alligator to be presenting additional data from our OPTIMIZE-1 trial," said Søren Bregenholt, PhD, CEO of Alligator Bioscience. "Mitazalimab’s differentiated efficacy and tolerability profile allows for the higher and more frequent doses which, when combined with chemotherapy like mFOLFIRINOX, increases the chances of demonstrating clinical benefit in the treatment of metastatic pancreatic cancer. We are very pleased with the successful completion of the Phase 1b section of the trial and we continue to make great progress with the enrollment for Phase 2."

The information was submitted for publication, through the agency of the contact person set out below, at 08:30 a.m. CEST on September 14, 2022.

On September 14, 2022 Phost’in Therapeutics (Montpellier, France), a clinical stage company focused on the discovery and development of N-glycosylation inhibitors for the treatment of cancer and other serious diseases, reported dosing of the first three patients in the Dose Escalation phase of the PhAST trial, an adaptive Phase I/II study in patients with advanced solid tumors evaluating the First-In-Class selective N-glycosylation inhibitor, PhOx430 (Press release, Phost’in, SEP 14, 2022, View Source [SID1234619532]). The study is operated with the scientific contribution of the Gianni Bonadonna Foundation which collaborated to the conception of the research protocol.

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PhAST trial will evaluate safety and pharmacodynamic effects of PhOx430 in patients. Additional objectives will include a preliminary evaluation of efficacy and the identification of biomarkers. The current dose escalation phase will eventually enroll two dozen of patients with non-selected tumour types. It will be followed by three expansion cohorts gathering patients with selected tumour types, including Glioblastoma multiforme (GBM), Triple-negative breast cancer (TNBC) and a selection of other solid tumour types, for which few therapeutic options exist.

Dr. Alain Herrera, CMO of Phost’in Therapeutics, said: "Dosing of first three patients marks an important milestone in the development of PhOx430. And beyond any scientific achievement, as a selective N-glycosylation inhibitor is administered for the 1st time in patients, it is a step ahead in the fight to overcome cancer and immune resistance with disrupting approaches". Dr. Luca Gianni, President of The Gianni Bonadonna Foundation, added "With the activation of both sites involved in the Dose Escalation Phase, a further step has been taken in this innovative first-in-human clinical trial, that could open new avenues for solid tumors therapy. With this in mind, Fondazione Gianni Bonadonna will continue collaborating with the PhAST Trial Team to achieve the best results for cancer patients’ benefit.".

First patients have been enrolled at the I.R.C.C.S. Ospedale San Raffaele in Milan, Italy, and at the Institute of Cancer of Montpellier (ICM), France. Dr. Diego Tosi, head of the Early Clinical Trial Unit-Medical Oncology Department and Principal Investigator at ICM, has been entrusted with the international direction of the first-in-human clinical trial.

The contract research organization ("CRO") Michelangelo Tech Srl (Milan, Italy) has been appointed by Phost’in to coordinate the PhAST trial. Owned by the Michelangelo Foundation with the aim of contributing to progress in cancer research and improving treatment options for tumors, Michelangelo Tech Srl provides extensive expertise in early phase clinical development, precisely to favor the rapid clinical application of new therapies. In parallel, Phost’in Therapeutics has selected Leads to Development (Paris, France), an agency with a strong reputation across Europe and the United States for regulatory and development expertise, to support product development strategy definition, operations and filings

About PhOx 430 treatment
The aberrant, complex and hypersialylated glycosylation of tumor cells is now recognized as a novel immune checkpoint, affecting key membrane receptors and masking tumor cells to the immune system, via the formation of complex abnormal glycan patterns operating as a shield. PhOx430 targets this aberrant glycosylation directly to the source through selective inhibition of a specific enzyme for a double antitumor effect, inducing simultaneously an anti-cancer immune response and the down regulation of the main receptors implicated in cancer progression. The program has demonstrated a significant antitumoral efficacy in several animal models, associated with a promising safety profile in regulatory preclinical studies. It is the first program from the Phost’ScreenTM platform that combines unique and patented chemical libraries with cutting-edge screening tools to produce selective nglycosylation inhibitors.

On September 14, 2022 Capstan Therapeutics, Inc., a biotechnology company dedicated to developing and delivering precise in vivo cell engineering to patients, reported that launched with $165 million in financing to build on the foundational insights of world-renowned leaders in mRNA and cell therapy, combining the power of cell therapy with the precision of genetic medicines to help bring safer, first-in-class medicines to more patients in multiple indications (Press release, Capstan Therapeutics, SEP 14, 2022, View Source [SID1234619529]).

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Capstan’s foundational precision in vivo engineering technology builds on research conducted in the laboratories of world-renowned mRNA and cell therapy scientists at the University of Pennsylvania.

Capstan’s funding includes a recently closed $102 million Series A financing led by Pfizer Ventures and joined by Leaps by Bayer, Eli Lilly and Company, Bristol Myers Squibb, Polaris Partners, Alexandria Venture Investments, and all existing investors, which follows a $63 million seed financing led by Novartis Venture Fund and OrbiMed and joined by RA Capital, and Vida Ventures in November 2021.

Advancing Breakthrough Therapies through Precision in vivo Engineering

The company plans to use the funds to further its mission of advancing the clinical promise of cell-based therapies by enabling precise in vivo engineering of cells with payloads necessary to benefit patients across multiple disease categories. Capstan’s modular platform leverages the biological and technological expertise of its founding scientists and includes proprietary targeted lipid nanoparticles (tLNP) technology, a suite of targeting moieties to mediate cell type-specific uptake, and disease-specific mRNA payloads aimed at directly engineering, or ablating pathogenic cells through in vivo generated CAR T cells.

Capstan is prioritizing programs based on the potential to transform clinical standards of care. The company’s initial efforts will focus on developing first-in-class in vivo CAR therapies, with the goal to deliver treatments in an outpatient setting, for patients who have diseases for which there are no effective treatments. Capstan also plans to leverage its precision delivery and engineering technology to advance new therapies for certain monogenic blood disorders.

Visionary Team of Accomplished Executives Poised to Deliver a Transformational Approach

Capstan is also pleased to announce that Laura Shawver, Ph.D., has joined the company as President and Chief Executive Officer. Dr. Shawver brings more than 20 years of experience in executive leadership positions in oncology and other serious diseases to this role, most recently serving as CEO of Silverback Therapeutics and President and CEO of Synthorx.

"Our ambition at Capstan is to invent new clinical paradigms through targeted in vivo reprogramming of cells," said Dr. Shawver. "Our founding scientific and operational team is purpose-built to advance programs to the clinic that unite decades of combined experience in groundbreaking CAR therapies with the latest advances in mRNA delivery technology. We are also fortunate to have a distinguished investor syndicate that understands the cell therapy landscape and recognizes the potential of this innovative approach. I am thrilled to lead this team as we work toward making this vision a reality for patients."

"Laura is an exceptional leader with a well-established track record in drug development and passion for addressing unmet needs in oncology and other serious diseases," said Michael Baran, Ph.D., Partner, Pfizer Ventures. "We are delighted to have someone of Laura’s caliber captain this exciting next chapter for Capstan to help unlock the potential of this transformative approach for patients."

Dr. Shawver joins an accomplished leadership team of industry veterans who have been at the forefront of cell and gene therapy, including Adrian Bot, M.D., Ph.D., Chief Scientific Officer, formerly Global Head and Vice President of Translational Medicine at Kite, a Gilead Company and previously Chief Scientific Officer at Kite Pharma; and Priya Karmali, Ph.D., Chief Technology Officer, who has over two decades of experience in the field of lipid nanoparticle mediated nucleic acid delivery technologies.

Building on Pioneering Work of World-Renowned Scientific Founders

"Capstan builds on a deep history of collaborative research in mRNA-enabled and CAR-based medicines by our incredible group of scientific founders," said Christian Homsy, M.D., MBA, Capstan’s founding CEO. "The company was established to deliver on the promise of cell-based medicines, and with Laura at the helm, is well-positioned to make rapid progress towards clinical evaluation."

The company’s scientific founders include several of the experts from the University of Pennsylvania who authored two landmark studies establishing preclinical proof-of-concept for non-viral, in vivo CAR-T therapy that Capstan plans to develop and advance toward the clinic. A 2019 Nature publication demonstrated the preclinical use of ex vivo CAR-T cell therapy against FAP, a fibrosis-related target. A follow-on study published in Science earlier this year built on these earlier results and demonstrated the production of functional CAR-T cells in vivo in a mouse model following a single IV administration of an mRNA encoding an anti-FAP CAR packaged in CD5-targeted-LNPs. The scientific founders span diverse areas of research expertise:

Preclinical translation – Jonathan Epstein, M.D. and Haig Aghajanian, Ph.D. (Dr. Aghajanian is now a Capstan employee.)
Cell engineering – Carl June, M.D. and Bruce Levine, Ph.D.
mRNA and targeted LNP technologies – Drew Weissman, M.D., Ph.D. and Hamideh Parhiz, Pharm.D., Ph.D.
Immunology and Fibrosis – Ellen Puré, Ph.D. and Steven Albelda, M.D.
"Capstan is uniting several recent life science technological advances in a manner that can hopefully unlock the potential of these technologies to develop new medicines for patients across a wider range of diseases," said Drew Weissman, M.D., Ph.D., Co-Founder of Capstan, who serves as the Roberts Family Professor in Vaccine Research and Director of the Penn Institute for RNA Innovation in the Perelman School of Medicine at the University of Pennsylvania, and co-recipient of the 2021 Lasker-DeBakey Clinical Medical Research Award.

"Research conducted at Penn demonstrates the tremendous promise of harnessing mRNA and targeted LNP delivery to train a patient’s body to make CAR-T cells in vivo, potentially creating new treatment options," said Jonathan Epstein, M.D., Chief Scientific Officer at Penn’s Perelman School of Medicine. "We believe this approach has the potential to make an important impact not only in oncology, but also in fibrosis and many other diseases. My fellow scientific co-founders and I all look forward to actively partnering with Capstan in our collaborative effort to develop medicines that may benefit patients around the world."

On September 14, 2022 Clarity Pharmaceuticals (ASX: CU6) ("Clarity"), a clinical stage radiopharmaceutical company with a mission to develop next-generation products that improve treatment outcomes for children and adults with cancer, reported that it has successfully imaged its first participants in the diagnostic 64Cu SAR-Bombesin trial (BOP) for patients with PSMA-negative prostate cancer in Australia (Press release, Clarity Pharmaceuticals, SEP 14, 2022, View Source [SID1234619524]).

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BOP (Copper-64 SAR Bombesin in Prostate Specific Membrane Antigen (PSMA) negative Prostate Cancer) is a Phase II investigator-initiated trial (IIT) in up to 30 patients led by Prof Louise Emmett at St Vincent’s Hospital, Sydney. The BOP trial is assessing the safety of 64Cu-SAR-Bombesin as well as looking at the diagnostic potential across two different groups of men:

Participants with suspected biochemical recurrence (BCR) of their prostate cancer who have negative PSMA positron emission tomography (PET) imaging scans or low PSMA expression disease.
Participants with metastatic castrate resistant prostate cancer (mCRPC) who are not eligible for PSMA therapy.
The trial is imaging with 64Cu SAR-Bombesin on the day of administration as well as at later timepoints.

Prof Louise Emmett (St Vincent’s Hospital Sydney), Principal Investigator in the BOP trial, commented, "We are very pleased to have recruited and imaged the first participants in this study. The SAR-Bombesin product is a promising target for a large patient population with a high unmet need and few treatments available to them. We are excited to now make the product available to a larger pool of patients under clinical trial conditions".

"SAR-Bombesin has already shown very promising data to date through a SAS case study1, demonstrating diagnostic imaging potential in PSMA-negative prostate cancer and highlighting potential utility of the product as a theranostic agent. We are now looking forward to further investigating the role of SAR-Bombesin in the better management of patients," said Prof Emmett.

Clarity’s Executive Chairman, Dr Alan Taylor, commented, "The commencement of this trial is yet another step forward in our collaboration with Prof Emmett and St Vincent Hospital Sydney as the BOP IIT is now our third clinical trial conducted in partnership. We are pleased that this collaboration has already resulted in changes in the management of the disease for patients in our own city of Sydney, as we head towards our ultimate goal of improving treatment outcomes for children and adults with cancer around the world."

"We believe that SAR-Bombesin has potential to provide large patient populations with accurate and precise detection and treatment of cancers that express the target and deliver clinical, environmental and logistical benefits enabled by the copper isotope pairing," said Dr Taylor.

Clarity’s Prostate Cancer clinical trial program overview

About SAR-Bombesin
SAR-Bombesin is a highly targeted pan-cancer radiopharmaceutical with broad cancer application. It targets the gastrin-releasing peptide receptor (GRPr) present on cells of a range of cancers, including but not limited to prostate, breast and ovarian cancers. GRPr is found in approximately 75-100% of prostate cancers, including prostate cancers that don’t express PSMA (PSMA-negative)2-6. The product utilises Clarity’s proprietary sarcophagine (SAR) technology that securely holds copper isotopes inside a cage-like structure, called a chelator. Unlike other commercially available chelators, the SAR technology prevents copper leakage into the body. SAR-Bombesin is a Targeted Copper Theranostic (TCT) that can be used with isotopes of copper-64 (Cu-64 or 64Cu) for imaging and copper-67 (Cu-67 or 67Cu) for therapy.

About Prostate Cancer
Prostate cancer is the second most common cancer diagnosed in men globally and the fifth leading cause of cancer death worldwide7. The National Cancer Institute estimates in 2022 there will be 268,490 new cases of prostate cancer in the US and around 34,500 deaths from the disease8.

Approximately 20% of prostate cancers with BCR are PSMA-PET negative9-12. These patients are therefore unlikely to respond to therapeutic PSMA-targeted products and currently have few treatment options available to them. Given the prostate cancer indication is one of the largest in oncology, there is a significant unmet medical need in this segment. The SAR-Bombesin product could offer valuable imaging and therapeutic options for not only PSMA negative patients, but also the large number of patients that have the target receptor on their cancers.

On September 13, 2022 METiS Therapeutics, a Boston-area company integrating drug discovery and delivery with AI and machine learning, reported they have entered a license agreement with Voronoi, Inc., a Korean company focused on precision medicine (Press release, METiS Therapeutics, SEP 13, 2022, View Source [SID1234648430]). Under the terms of this license agreement, METiS will receive exclusive license to develop and commercialize Voronoi’s pan-RAF inhibitor program worldwide. In exchange, Voronoi will receive up to $1.7 million in upfront cash and success-based near-term discovery milestones. Voronoi will also be eligible for success-based payment up to $480.5 million in development, regulatory and sales milestones and tiered royalties based on annual net sales.

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"We view this program as a potential best-in-class asset addressing high unmet clinical needs for Class II and Class III BRAF mutant cancer patients, particularly those with CNS metastasis," said Chris Lai, CoFounder and CEO of METiS Therapeutics. "We see it as a compelling proof-of-concept opportunity for our AiTEM platform to improve compound pharmacokinetics and deliver a differentiated profile, including CNS penetration. In addition, we view this as a foundational asset for our oncology portfolio."

BRAF is a protein kinase involved in cancer cell growth and BRAF mutations are the most common mutation found in tumor cells[1]. While several BRAF v600E inhibitors have been approved, this mutation only represents about 45% of total BRAF mutations, compared to Class II and III mutations which represent 55 percent of total BRAF mutations. This underscores the need for new therapeutic options in this space.

"We developed our structurally distinguished type II pan-RAF inhibitor to address unmet medical needs, and this partnership brings us closer to our goal of delivering this candidate to patients," says Daekwon Kim, CEO of Voronoi. "We are excited to partner with METiS’ seasoned team to continue on development of our pan-RAF inhibitor." added Daekwon."We developed our structurally distinguished type II pan-RAF inhibitor to address unmet medical needs, and this partnership brings us closer to our goal of delivering this candidate to patients," says Daekwon Kim, CEO of Voronoi. "We are excited to partner with METiS’ seasoned team to continue on development of our pan-RAF inhibitor." added Daekwon.

This news follows METiS’ announcement that the company had joined the Roche Accelerator earlier this year. In December, METiS closed an $86 million Series A financing round. The company recently leased 14,000 square feet of mixed office and laboratory space at 101 Cambridgepark Drive in Cambridge, MA.14,