Synnovation Therapeutics Launches with $102 Million to Advance Clinical-Stage Pipeline of Precision Therapies Targeting Highly Validated Disease Pathways

On January 24, 2024 Synnovation Therapeutics, a precision medicine company developing small molecule therapies optimized to achieve best-in-class pharmacology against highly validated disease targets, reported to have launched with a $102 million Series A (Press release, Synnovation Therapeutics, JAN 24, 2024, View Source [SID1234639467]). The financing was led by Third Rock Ventures with participation from Nextech, Lilly Asia Ventures, Sirona Capital and Cormorant Asset Management. Synnovation was founded by a world-class medicinal chemistry team with a track record of developing best-in-class therapeutics. Proceeds will fund the advancement of the company’s clinical and preclinical pipeline, including SNV1521 and SNV4818, as well as additional programs.

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Synnovation’s pipeline is built around highly validated precision oncologic targets where greater potency, selectivity and optimized pharmaceutical properties have the potential to address liabilities in existing standards of care, and meaningfully improve patient outcomes. The company’s lead program, SNV1521, is a potentially best-in-class, potent, highly selective and CNS penetrant PARP1 inhibitor. PARP1 isoform selective inhibition is emerging as one of the most exciting new approaches to combat solid tumors, offering the potential to create new and well-tolerated therapeutic approaches that attack genetic and pharmacologic vulnerabilities of cancer. The company is initiating a Phase I study and anticipates dosing its first patient in the coming weeks. Synnovation’s second program targets oncogenic PI3K-alpha, leveraging multiple distinct mutant-selective approaches. The company’s first development candidate, SNV4818, is a potent, and potentially best-in-class mutant selective PI3K-alpha inhibitor. SNV4818 is differentiated from competitor molecules by virtue of its excellent selectivity for H1047X and moderate selectivity over relevant E545/542X mutants.

Synnovation was founded by a world-class medicinal chemistry team with drug discovery expertise and a track record of developing best-in-class therapeutics. While at Incyte, the management team worked together for more than a decade and contributed to the discovery of five approved drugs including Jakafi (ruxolitinib), Olumiant (baricitinib), Pemazyre (pemigatinib), Tabrecta (capmatinib), and Opzelura (topical ruxolitinib). These novel medicines have become important treatments for many diseases, including myelofibrosis and polycythemia vera, graft-vs-host disease, rheumatoid arthritis, cholangiocarcinoma, non-small-cell lung cancer, atopic dermatitis, and vitiligo.

"At Synnovation, we have assembled a top-notch team dedicated to fostering a multidisciplinary and collaborative approach as advocated by my mentor Dr. Ralph F. Hirschman, who ardently believed that the collaboration between creative chemists and outstanding biologists could lead to remarkable discoveries," said Wenqing Yao, Ph.D., chief executive officer of Synnovation. "Our goal is to develop best-in-class therapies, ultimately aiming to enhance the lives of patients. We look forward to advancing in the clinic with SNV1521, a novel PARP1 selective inhibitor, as we continue to grow our potential best-in-class pipeline of agents."

"Synnovation was founded by one of the most accomplished medicinal chemistry teams in biopharma," said Reid Huber, Ph.D., board member at Synnovation and partner at Third Rock Ventures. "This highly experienced leadership team has a rich history of successful drug discovery and development, and a passion to build further on this success. We are excited to be a part of this company and look forward to what this stellar team will accomplish as it takes its decades of experience and applies them to an entirely new set of R&D challenges."

Synnovation Leadership

Wenqing Yao, Ph.D., Founder and CEO, was most recently EVP and Head of Discovery Chemistry at Incyte, where he spent 19 years. While at Incyte, Dr. Yao led a chemistry team which discovered more than 30 clinical compounds and five approved drugs including Jakafi, Olumiant, Pemazyre, Tabrecta, and Opzelura. Dr. Yao joined Incyte in early 2002 as one of the founding scientists and contributed to the establishment of Incyte’s world-class small molecule drug discovery group.
Liangxing Wu, Ph.D., Co-Founder and SVP Drug Discovery, was most recently Executive Director, Medicinal Chemistry at Incyte, where he spent nearly 10 years working in drug discovery and contributed to the discovery of multiple clinical compounds and FDA approved drug Pemazyre.
Phillip Liu, Ph.D., SVP Head of Biology, has more than 20 years of experience in biotech and pharma including 17 years at Incyte, where he led a cell and molecular biology group that supported Incyte’s discovery pipeline and collaborated closely with Dr.s. Yao and Wu on FGFR and PD-L1 small molecule programs. He was most recently Executive Director, Oncology, Kymera Therapeutics.
Kevin O’Hayer, M.D., Ph.D., SVP Head of Clinical Development is an Medical Oncology physician-scientist who most recently led the Oral PD-L1 program as VP, GPH at Incyte. Dr. O’Hayer also developed clinical programs with multiple JAK inhibitors in inflammatory conditions and COVID-19.
The Board of Directors at Synnovation includes Ting Feng, Ph.D., Sirona Capital; Reid Huber, Ph.D., Third Rock Ventures; Judith Li, Lilly Asia Ventures (observer); Jigar Raythatha, Third Rock Ventures; Thilo Schroeder, Ph.D., Nextech; Liangxing Wu, Ph.D., Synnovation; and Wenqing Yao, Ph.D., Synnovation.

UroGen Initiates Submission of a Rolling NDA to the FDA for UGN-102

On January 24, 2024 UroGen Pharma Ltd. (Nasdaq: URGN), a biotech company dedicated to developing and commercializing novel solutions that treat urothelial and specialty cancers, reported the submission of the Chemistry, Manufacturing, and Controls (CMC) section of the New Drug Application (NDA) for UGN-102 (mitomycin) for intravesical solution to the U.S. Food and Drug Administration (FDA) (Press release, UroGen Pharma, JAN 24, 2024, View Source [SID1234639452]).

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"The submission of the CMC portion of the NDA for UGN-102 marks a significant milestone for UroGen and underscores our dedication to advancing innovative therapies for the benefit of individuals grappling with low-grade, intermediate-risk non-muscle invasive bladder cancer," said Liz Barrett, President and CEO, UroGen. "We look forward to working closely with the FDA throughout the review process and remain steadfast in our commitment to address unmet medical needs in the uro-oncology space and advance patient care."

The objective of the rolling NDA for UGN-102 is to facilitate early engagement with the FDA, and a more efficient and timely review of the NDA. Based on its agreement with the FDA, UroGen will complete the submission of the rolling NDA for UGN-102 in 2024 with a potential FDA decision as early as the first quarter of 2025.

The CMC section of a regulatory submission typically includes information about the drug product such as its physicochemical properties, formulation, methods of manufacture, specifications, stability data, and analytical methods used to test the product.

About UGN-102

UGN-102 (mitomycin) for intravesical solution is an innovative drug formulation of mitomycin, currently in Phase 3 development for the treatment of low-grade, intermediate-risk, non-muscle invasive bladder cancer (LG-IR-NMIBC). Utilizing UroGen’s proprietary RTGel technology, a sustained release, hydrogel-based formulation, UGN-102 is designed to enable longer exposure of bladder tissue to mitomycin, thereby enabling the treatment of tumors by non-surgical means. UGN-102 is delivered to patients using a standard urinary catheter in an outpatient setting. Assuming positive findings from the durability of response endpoint from the ENVISION Phase 3 study, UroGen anticipates completing its NDA submission for UGN-102 in 2024 with a potential FDA decision as early as the first quarter of 2025.

VerImmune Inc announces the continued growth of its patent portfolio for Virus-inspired Particle (ViP) based Cancer treatment

On January 24, 2024 VerImmune, Inc., a biotechnology company specializing in Virus-inspired Particle modalities for cancer treatment and other disease areas, proudly reported the issuance of its third U.S. Patent from the U.S. Patent and Trademark Office (USPTO) (Press release, VerImmune, JAN 24, 2024, View Source [SID1234639454]).

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The newly issued patent, U.S. Patent No. 11,858,964 B2, appropriately titled "Virus-inspired Compositions and Methods of Redirecting Pre-existing Immune Responses for the Treatment of Cancer," provides a comprehensive layer of protection and support for VerImmune’s ViP proprietary technology platform. This patent includes a novel ViP composition of matter, along with innovative methods for manufacturing and utilizing the technology in cancer treatment. This patent will safeguard the technology platform until at least 2041, which offers an extensive period of exclusivity and protection.

Additionally, VerImmune is also pleased to also announce that the USPTO has issued a notice of allowance for a continuation patent building upon the success of its previously issued patent, U.S. Patent No. 11,285,203, entitled "Chimeric virus-like particles and uses thereof as antigen-specific redirectors of immune responses," This new additional patent will provide additional claim scope, broadening the protection of VerImmune’s first issued patent family.

Collectively, these latest developments further solidify VerImmune’s intellectual property moat at the forefront of cutting-edge cancer treatment technologies.

VerImmune’s revolutionary platform is currently focused on redirecting the body’s pre-existing T-cell memory against pathogens, effectively harnessing its power to combat cancer. With the potential to target multiple types of cancer, the technology’s versatility arises from the near-universal nature of pre-existing responses triggered by childhood vaccines and past infections. As a result, VerImmune’s patented technology holds promise for broad applications in cancer treatment, marking a significant stride towards more effective and inclusive solutions.

CytomX Therapeutics Announces FDA Clearance of IND Applications for CX-2051, a Probody® Antibody Drug Conjugate (ADC) Targeting EpCAM and CX-801, a Conditionally Activated Interferon Alpha-2b

On January 24, 2024 CytomX Therapeutics, Inc. (Nasdaq: CTMX), a leader in the field of conditionally activated, localized biologics, reported that it has received clearance from the U.S. Food and Drug Administration (FDA) for its Investigational New Drug (IND) applications for the conditionally activated Probody therapeutics CX-2051, an EpCAM-directed ADC, and CX-801, a dually-masked version of interferon-alpha 2b (Press release, CytomX Therapeutics, JAN 24, 2024, View Source [SID1234639455]). CX-2051 has been cleared for the initiation of Phase 1 dose escalation in solid tumors with known EpCAM expression and CX-801 has been cleared for the initiation of Phase 1 dose escalation in solid tumors including melanoma, renal, and head and neck squamous cell carcinoma. Both programs are expected to start Phase 1 studies in the first half of 2024.

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"CX-2051 and CX-801 have the potential to address major unmet needs in oncology and we are excited to advance these programs into Phase 1 clinical studies. CX-2051 is an ADC conjugated to a next-generation topoisomerase-1 inhibitor payload that we believe is tailored to certain EpCAM-expressing tumors, including colorectal cancer," said Wayne Chu, M.D., chief medical officer of CytomX Therapeutics. "CX-801 is designed to overcome previous limitations of interferon-directed therapies due to systemic toxicity and establish CX-801 as a cornerstone of combination regimens, including with checkpoint inhibitors, across a wide range of tumor types," continued Dr. Chu.

"The parallel advancement of these programs toward the clinic demonstrates the continued high productivity of the CytomX team and the versatile, multi-modality nature of our Probody platform. The product design principles behind CX-2051 and CX-801 integrate over a decade of continuous innovation and experience at CytomX," said Sean McCarthy, D.Phil., chief executive officer and chairman of CytomX Therapeutics. "We look forward to the clinical initiation of these programs as we enter a potentially milestone-rich period for the company in 2024 and 2025."

About CX-2051

EpCAM is a high potential oncology target that has been clinically validated by locally administered, previously approved cancer therapies. However, to date, efforts to generate systemically administered anti-EpCAM therapeutics have not been successful due to toxicities in certain epithelial tissues, notably in the gastrointestinal tract. CX-2051, a conditionally activated ADC, is tailored to optimize the therapeutic index for EpCAM-expressing cancers. The cytotoxic payload utilized in CX-2051 is a derivative of camptothecin, a topoisomerase-1 inhibitor, a class of drug that has shown potent clinical anti-cancer activity in the ADC context for multiple targets. CX-2051 has demonstrated a wide predicted therapeutic index and strong preclinical activity and tolerability in multiple preclinical models, including colorectal cancer. Phase 1 clinical initiation in EpCAM expressing solid tumors is expected in the first half of 2024. Further details on the design and preclinical optimization of CX-2051 can be found here:

Link to 2023 World ADC Conference presentation

About CX-801

Interferon-alpha 2b is an immunotherapeutic cytokine that has demonstrated clinical activity and gained regulatory approval previously in multiple cancer types, including metastatic melanoma, renal cancer and bladder cancer. IFNα2b provides a potentially superior approach to activating anti-tumor immune responses compared to other cytokines. CX-801 is a dually masked, conditionally activated version of IFNα2b that has the potential to become a cornerstone of combination therapy for a wide range of tumor types, including in traditionally immuno-oncology sensitive as well as insensitive (cold) tumors. Phase 1 initiation for CX-801 solid tumors including melanoma, renal, and head and neck squamous cell carcinoma anticipated in the first half of 2024. Further details on the design and preclinical optimization of CX-801 can be found here:

Link to 2023 SITC (Free SITC Whitepaper) poster

Genome & Company Announces Positive Topline Results from Phase 2 Clinical Trial of Combination of GEN-001 and Bavencio® for the Treatment of Gastric Cancer Poster presented at ASCO GI

On January 24, 2024 Genome & Company (KOSDAQ: 314130), a clinical stage biotech leading in microbiome therapeutic development reported on January 18th (local time) that a poster was presented on the positive topline results from the phase 2 clinical trial (NCT05419362) in gastric cancer of its microbiome immunotherapy, GEN-001 at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Gastrointestinal Cancers Symposium (ASCO GI 2024) (Press release, Genome & Company, JAN 24, 2024, View Source;company-announces-positive-topline-results-from-phase-2-clinical-trial-of-combination-of-gen-001-and-bavencio-for-the-treatment-of-gastric-cancer-poster-presented-at-asco-gi-302042094.html [SID1234639456]).

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GEN-001 is an oral therapeutic candidate consisting of a single strain of Lactococcus lactis, and the phase 2 clinical trial for gastric cancer was conducted in combination with avelumab (Bavencio) developed and commercialized by Merck KGaA, Darmstadt, Germany.

The clinical trial is being conducted at 6 domestic institutions in South Korea on 42 patients with PD-L1-positive advanced gastric cancer or gastroesophageal junction adenoma cancer who has failed second-line or later standard of care treatment regardless of prior immunotherapy. The positive headline results of the interim analysis of the Phase 2 clinical trial were made public in May of last year, and detailed topline results of the Phase 2 clinical trial conducted to date were disclosed for the first time at this ASCO (Free ASCO Whitepaper) GI 2024.

As a result of the efficacy evaluation of 42 patients participating in the phase 2 clinical trial, partial responses (PRs) were observed in 7 out of 42 patients. Furthermore, 3 out of 8 patients among 42 patients who were previously treated by immunotherapy experienced PRs (overall response rate, ORR 37.5%).

In addition, the topline results revealed the median progression free survival (PFS) at 1.7 months and the median overall survival (OS) at 7.9 months.

Under the current frontline immunotherapy landscape in gastric cancer, GEN-001 and Bavencio combination may become an attractive therapeutic option in the salvage setting of gastric cancer. Treatment-related adverse events (TRAEs) were observed in 14 patients out of 42 patients, and only 2 patients experienced grade 3 TRAEs including anemia, fatigue, and pneumonitis. Overall, this combination showed manageable safety and tolerability.

Prof. Jeeyun Lee (M.D.) from the Department of Hemato Oncology at Samsung Medical Center, the coordinating investigator of the study stated, "while there are limited treatment options available for patients with metastatic gastric cancer, combination of GEN-001 and avelumab demonstrated favorable therapeutic effects leading to an extended survival. The overall response rate (ORR) of 37.5% is particularly promising among PD-L1-positive refractory patients to prior immunotherapy. We intend to further validate these results in subsequent clinical studies to establish this treatment regimen as a viable third-line treatment." Expressing enthusiasm, she added, "we are excited that this marks the first clinical study to showcase the potential of microbiome therapeutics in the treatment of gastric cancer."

Dr. Jisoo Pae, CEO of Genome & Company, said, "we are incredibly pleased by our presentation at ASCO (Free ASCO Whitepaper) GI 2024 on the topline data of the phase 2 clinical trial for gastric cancer with our microbiome immuno-oncology treatment, GEN-001. Based on the results, we can confirm not only the results of exceeding the primary endpoints, but also compelling clinical benefits compared to the previously published Bavencio monotherapy data". He continued, "we plan to establish a future development strategy from obtaining further data in response duration, biomarker analysis, and overall survival."

Meanwhile, in addition to the ongoing clinical trials in combination with Bavencio, GEN-001 is currently in another phase 2 combination clinical trial for biliary tract cancer with pembrolizumab (Keytruda), a cancer immunotherapy drug from MSD (a tradename of Merck & Co., Inc., Kenilworth, N.J., USA). Through combination therapy clinical trials with anti-PD-1 and PD-L1 immunotherapy drugs, Genome & Company aims to develop treatments in overcoming the resistance to immunotherapy.