On April 11, 2023 K36 Therapeutics ("K36"), a privately held biotechnology company developing KTX-1001, an investigational small molecule methyltransferase inhibitor of multiple myeloma SET domain known as MMSET, announced today that the first patient has been dosed in its Phase 1 clinical trial earlier this year (Press release, K36 Therapeutics, APR 11, 2023, View Source [SID1234629972]). KTX-1001 is an oral, first-in-class, selective and potent MMSET catalytic inhibitor that suppresses H3K36me2 in patients with relapsed and refractory multiple myeloma. The K36-MMSET-001 Phase 1 clinical trial is designed to assess the safety, tolerability, pharmacology, and initial clinical activity of KTX-1001 (NCT05651932).

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"We are thrilled to have reached this clinical milestone and appreciate our ongoing partnership with Sarah Cannon Research Institute (SCRI) at Tennessee Oncology," said Terry Connolly, Ph.D., Chief Executive Officer of K36. "KTX-1001 has not only demonstrated encouraging preclinical activity and a favorable tolerability profile, but it also addresses unmet need for patients who have received other standard of care therapies available to patients suffering from multiple myeloma. We look forward to working with all our sites, investigators, and study teams to efficiently enroll our Phase 1 clinical trial."

The first patient has been dosed in Nashville, TN by the Lead Principal Investigator and Director of Myeloma Research for SCRI at Tennessee Oncology, Jesus Berdeja, MD, who stated, "There still remains a need for new personalized therapies to treat multiple myeloma and novel precision therapeutics like KTX-1001 offer a potential solution to address the challenges seen in high-risk subsets like translocation t(4;14). We are delighted to be the first institution to advance this first-in-class agent into the clinic with K36."

K36 has also appointed Michael Heffernan as an Independent to the company’s Board of Directors. "We are pleased to welcome Michael Heffernan to the Board," said Dr. Connolly. "Michael’s late-stage development and commercial experience will complement our exceptionally strong scientific board as we further our business and pursue our mission to expand therapeutic pursuits that serve patients."

Michael brings over 30 years of experience in building and leading development stage and commercial companies in the biopharmaceutical space. "It is an exciting time at K36. I am excited to work with the Board, Terry, and the talented K36 team to further the development and commercialization plan of KTX-1001," noted Mr. Heffernan.

Mr. Heffernan is an advisor, investor, and board member of numerous public and private biopharmaceutical companies. He began his career at Eli Lilly and Company, where he served in numerous sales and marketing roles. He then served a variety of roles, including President and CEO of Collegium since its inception, co-founder and CEO of Clinical Studies Ltd. (acquired by PhyMatrix Corp), Co-Founder and Chairman/CEO of Avenge Bio, Inc., Chairman/CEO of Onset Dermatologics, and Founder and Chairman of Collegium Pharmaceutical (COLL). He currently is a member of the Board of Directors of Biohaven (BHVN), Collegium (COLL), Trevi (TRVI), and Synlogic (SYBX).

Mr. Heffernan was named E&Y Entrepreneur of the Year, Northeast Regional Winner in 2016. He is a registered pharmacist and earned his B.S. Degree in Pharmacy from the University of Connecticut.

About KTX-1001

KTX-1001 is a novel, first-in-class, potent, and selective catalytic inhibitor of the H3K36 methyltransferase MMSET. It is an investigational and orally administered small molecule being developed initially for the treatment of relapsed and refractory multiple myeloma, with a focus on patients with the genetic translocation t(4;14).

On April 11, 2023 Beactica Therapeutics AB, the Swedish precision oncology company, reported that its LSD1 programme has been selected for a poster presentation at the American Association for Cancer Research (AACR) (Free AACR Whitepaper)’s Annual Meeting 2023 (Press release, Beactica, APR 11, 2023, View Source [SID1234629971]). The conference will take place on April 14-19, 2023 at the Orange County Convention Center in Orlando, Florida.

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Dr Konrad Koehler, Head of Discovery, will present a poster entitled Potentiation of Immunotherapy by LSD1 Modulation on Sunday April 16, 2023, at 1:30 PM – 5:00 PM. The location is at the Orange County Convention Center, Section 24, Abstract Presentation Number: 705. The session category is Immunology.

Beactica Therapeutics’ poster presentation will include new positive results with BEA-17 from in vitro and in vivo studies, including potentiation of anti-PD1 checkpoint inhibitors in a syngeneic animal model of colon cancer (CT26) and potentiation of standard of care (radiation + temozolomide) in a syngeneic animal model of glioblastoma (GL261).

BEA-17 was recently granted Orphan Drug Designation by the U.S. Food and Drug Administration (FDA) for the treatment of glioblastoma (GBM).

Organised by the American Association for Cancer Research (AACR) (Free AACR Whitepaper), the AACR (Free AACR Whitepaper) Annual Meeting is the largest and most important cancer drug discovery event in the world. It has an anticipated attendance of more than 20 000 scientists, clinicians, advocates, and other attendees. The event spans integrative cancer science, global impact, individualised patient care and showcases the best and most up-to-date cancer science available.

About BEA-17

BEA-17 is a first-in-class small molecule targeted degrader (non-PROTAC) of the epigenetic enzyme LSD1 and its co-factor CoREST. The compound has shown promising preclinical in vivo potentiation of immune-modulating treatments in several cancer forms, including anti-PD1 checkpoint inhibitors in syngeneic models of colon cancer (CT26) and standard of care (temozolomide and radiation) in syngeneic models of glioblastoma (GL261). Pharmacokinetic studies of BEA-17 show good blood-brain-barrier penetration and oral availability. BEA-17 is investigational and not approved anywhere globally. Its efficacy and safety in humans have not been established. BEA-17 has been granted Orphan Drug Designation by the U.S. Food and Drug Administration (FDA) for the treatment of glioblastoma (GBM).

On April 11, 2023 HotSpot Therapeutics, Inc., a biotechnology company pioneering the discovery and development of oral, small molecule allosteric therapies for the treatment of cancer and autoimmune diseases, reported the recent initiation of dosing of HST-1011 in its Phase 1/2 clinical trial in patients with advanced solid tumors (Press release, HotSpot Therapeutics, APR 11, 2023, View Source [SID1234629970]). HST-1011 is an orally bioavailable, potent, selective small molecule allosteric inhibitor of casitas B-lineage lymphoma-B (CBL-B).

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"Dosing of the first patient with HST-1011 is an important milestone for HotSpot signifying our evolution into a clinical-stage company with the first-in-human dosing of a product candidate derived from our proprietary Smart Allosterydrug discovery platform," said Tim Reilly, Ph.D., Chief Development Officer of HotSpot. "Importantly, we believe that HST-1011, as a highly potent and selective inhibitor of the long sought after target CBL-B, may represent an important new immunotherapy treatment option for cancer patients."

The Phase 1/2 study of HST-1011 is an open-label clinical study designed to evaluate HST-1011 alone and subsequently in combination with Regeneron’s anti-PD-1 therapy, Libtayo (cemiplimab), in patients with advanced solid tumors that are relapsed on or are refractory to anti-PD(L)-1 or standard of care therapies. Additional information on this clinical trial can be found on www.clinicaltrials.gov (NCT05662397). The combination therapy component of the study is enabled by a clinical supply agreement with Regeneron for provision of Libtayo.

"Despite tremendous progress in the field of immuno-oncology (I-O), significant unmet need persists for patients with advanced solid tumors, as many cancers are found to be unresponsive to or lack durable responses following treatment with currently available therapies," said Jason Luke, M.D., F.A.C.P., Director of the Immunotherapy and Drug Development Center at the University of Pittsburgh Medical Center’s Hillman Cancer Center and the lead Principle Investigator on HotSpot’s ongoing Phase 1/2 clinical study. "We believe CBL-B’s role as a master regulator of immune cell activation presents a differentiated therapeutic opportunity. We are excited to explore this novel mechanism and new I-O treatment in collaboration with HotSpot and the other investigators and sites participating in this trial."

HotSpot will be presenting the HST-1011 first-in-human Phase 1/2 clinical trial design at the upcoming American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2023, taking place in Orlando, Florida, during the Clinical Trials in Progress poster session. The details for the presentation are as follows:

Title: Phase 1/2 study of HST-1011, an oral CBL-B inhibitor, alone and in combination with anti-PD-1 in patients with advanced solid tumors
Session Title: Phase I and First-in-Human Clinical Trials in Progress
Session Date and Time: Tue., Apr. 18, 1:30-5:00 PM ET
Location: Poster Section 46
Poster Board Number: 14
Abstract Number: CT251

About HST-1011
HST-1011 is an investigational orally bioavailable, selective, small molecule allosteric inhibitor of CBL-B, an E3 ubiquitin protein ligase critically involved in immune cell response. Because CBL-B functions as a master regulator of effector cell (T cell and natural killer cell) immunity, its inactivation removes its endogenous negative regulatory functions to substantially enhance anti-tumor immunity. Preclinical data has demonstrated HST-1011’s ability to bind to and inhibit a natural hotspot on CBL-B, yielding the activation and propagation of a targeted anti-tumor immune response. Enabled by HotSpot’s proprietary Smart Allostery platform, HST-1011 is designed with tight binding, low nanomolar potency, a slow dissociation rate from the target to enable sustained pharmacology, and greater selectivity for CBL-B relative to C-CBL.

On April 11, 2023 OnCusp Therapeutics, a global biopharmaceutical company dedicated to transforming cutting-edge preclinical innovation into clinically validated treatments for cancer patients worldwide, reported that the preclinical data on its lead program CUSP06 will be presented during the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2023, taking place April 14-19, 2023, in Orlando, Florida (Press release, OnCusp Therapeutics, APR 11, 2023, View Source [SID1234629969]).

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The poster presentation will showcase data demonstrating that CUSP06, a high affinity anti-CDH6 Antibody Drug-Conjugate (ADC) with an exatecan payload (DAR8), shows potent anti-tumor activity in multiple preclinical models, demonstrates significant differentiation from a DXd-payload competitor, and is well tolerated in mice, rats and cynomolgus monkeys.

POSTER PRESENTATION DETAILS

Title: CUSP06/AMT-707, a new CDH6-targeting antibody-drug conjugate, demonstrates potent antitumor activity in preclinical models

Session Category: Experimental and Molecular Therapeutics
Session Date and Time: Wednesday Apr 19, 2023, 9:00 AM – 12:30 PM
Location: Poster Section 21
Poster Board Number: 27
Published Abstract Number: 6320

The abstract is available here and the Poster will be available on the OnCusp website shortly after the presentation.

"We are very excited to present data highlighting the exciting preclinical profile of CUSP06, a differentiated, potential global second-in-class CDH6 ADC, as we pivot to become a clinical stage company this year" stated Eric Slosberg, PhD, Chief Development Officer and co-founder of OnCusp Therapeutics.

About CUSP06:

CUSP06, a preclinical-stage CDH6 ADC, is composed of a proprietary antibody with high CDH6 binding affinity, a protease cleavable linker, and an exatecan payload (a potent and clinically validated topoisomerase-1 inhibitor). The linker is specially designed to complement the exatecan payload, generating a highly stable and homogenous ADC. The payload is a weak substrate for BCRP/Pgp. In preclinical data, this linker/payload has been shown to enable a stronger "bystander effect" than competitor ADCs. CUSP06 has a drug-to-antibody ratio of 8. OnCusp obtained the exclusive global rights (ex-China) to lead the development and commercialization of CUSP06, from Multitude Therapeutics.

On April 11, 2023 Quadriga BioSciences, a clinical-stage oncology company developing QBS10072S (QBS72S) for the targeted treatment of cancer, reported the dosing of the first subject in a Phase 2 study evaluating QBS72S for the treatment of brain metastases of breast cancers (Press release, Quadriga BioSciences, APR 11, 2023, View Source [SID1234629968]).

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"The treatment of brain metastases is a significant unmet need in oncology, as no approved therapies exist," said Gordon Ringold, Ph.D., Chief Executive Officer of Quadriga BioSciences. "With its ability to cross the blood brain barrier and target cancer cells, QBS72S has the potential to improve outcomes in these patients. We look forward to investigating this more closely with our colleagues at Stanford Medicine."

Most therapies for breast cancer have limited efficacy when metastasized to the brain, due in part to the inability for current chemotherapeutics to cross the blood brain barrier (BBB) in sufficient concentrations.

"Breast cancer is one of the most common tumors to metastasize to the brain. Breast cancer brain metastases worsen prognosis, negatively affect quality of life, and currently available treatments are limited," said Melanie Hayden Gephart, M.D., Professor of Neurosurgery at Stanford Medicine, co-director of the Stanford Brain Tumor Center, and Principal Investigator of the Phase 2 clinical study. "QBS72S has shown promise in preclinical studies due to its targeted mechanism of action. I look forward to the opportunity to investigate this compound for patients in need."

QBS72S is also being investigated as a potential glioblastoma treatment in the Phase 2 INSIGhT study at the Dana-Farber Cancer Institute (find more information here). The two Phase 2 studies are each funded by Small Business Innovation Grants (SBIR). The breast cancer study received initial support from the California Breast Cancer Research Program.

About QBS72S

QBS72S is a novel, first-in-class chemotherapeutic agent that mimics an aromatic amino acid for cellular uptake by the amino acid transporter LAT1 (L-type amino acid transporter 1) thereby enabling the drug to cross the blood brain barrier (BBB) as well as to selectively target numerous types of rapidly growing cancer cells. Once inside the cell QBS72S causes double-stranded DNA breaks resulting in cell death. Most aggressive cancers express high LAT1, which is commonly associated with poor prognoses.1

About the Study

The Phase 2 open-label clinical trial is designed to assess the safety, tolerability and efficacy of QBS72S in patients with brain metastases from breast cancer. The study will recruit up to 35 patients with the primary objective of determining preliminary efficacy through overall response rate. Secondary endpoints include measurement of progression free survival, overall survival, duration of response, and adverse events.

Please refer to www.clinicaltrials.gov [NCT05305365] for additional clinical trial details.