On July 5, 2023 Verastem Oncology (Nasdaq: VSTM) (the "Company"), a biopharmaceutical company committed to advancing new medicines for patients with cancer, reported that it has finalized with the U.S. Food and Drug Administration (FDA) the design of its confirmatory Phase 3 trial to evaluate the combination of avutometinib and defactinib for the treatment of recurrent low-grade serous ovarian cancer (LGSOC) (Press release, Verastem, JUL 5, 2023, View Source [SID1234633069]). RAMP 301, a randomized global confirmatory trial, will evaluate the efficacy and safety of avutometinib and defactinib versus standard of care (SOC) chemotherapy and hormonal therapy in patients with recurrent LGSOC. RAMP 301 is expected to begin enrollment in the second half of this year.

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RAMP 301 is the follow-up confirmatory study for full approval in recurrent LGSOC. The Company intends to file for Accelerated FDA Approval for the combination of avutometinib and defactinib based on mature data from the Company’s Phase 2 registration-directed RAMP 201, together with the results of the investigator-initiated FRAME trial. The Company recently reported results of Part A of RAMP 201 including confirmed objective response rates (ORR) by blinded independent central review of 45% (13/29; 95% CI: 26%,64%) with a tolerable safety profile.​

"We are pleased to partner with GOG and ENGOT and announce the final study design for RAMP 301, another important milestone in advancing our avutometinib and defactinib program and bringing us closer to addressing the unmet needs of patients living with LGSOC," said Brian Stuglik, Chief Executive Officer, Verastem Oncology. "This trial builds on the encouraging results of Part A of the RAMP 201 trial and our breakthrough therapy designation, after one or more prior lines of therapy, and we are committed to bringing the first FDA-approved therapy for LGSOC to patients as quickly as possible."

RAMP 301 is an international collaboration between The GOG Foundation, Inc. (GOG) and the European Network of Gynaecological Oncological Trial groups (ENGOT) sponsored by Verastem Oncology. The trial will enroll approximately 270 patients who will be randomized to either the combination of avutometinib and defactinib or SOC chemotherapy (pegylated liposomal doxorubicin, paclitaxel, topotecan) or hormone therapy (letrozole, anastrozole). Selection of the SOC regimen will be based on the preference of the investigator. The primary endpoint is progression free survival (PFS) by Blinded Independent Central Review. Secondary endpoints include overall response rates, duration of response​, disease control rate, safety and tolerability, patient reported outcomes and overall survival. The RAMP 301 trial will be led globally and in the U.S. by Rachel Grisham, MD, Section Head, Ovarian Cancer and Director, Gynecologic Medical Oncology at Memorial Sloan Kettering Cancer Center in Westchester, NY. Susana Banerjee, MBBS, MA PhD, FRCP, global and lead investigator of the RAMP 201 study, Consultant Medical Oncologist at The Royal Marsden NHS Foundation Trust and Team Leader in Women’s Cancers at The Institute of Cancer Research, London, will be leading the RAMP 301 trial in Europe.

Financial Update

As of March 31, 2023, Verastem Oncology had cash and short-term investments of $111.2 million. With the net proceeds from the underwritten public offering completed in June 2023 of approximately $91.5 million after deducting estimated underwriting discounts and commissions and estimated offering expenses, the Company has pro-forma cash and short-term investments as of March 31, 2023 of approximately $202.7 million.

Recent historical operating expenses have ranged between $16.0M — $20.0M per quarter, which the Company does not anticipate will change significantly in the near term as the RAMP 301 trial commences.

Dr. Banerjee and Dr. Grisham have consulting relationships with Verastem Oncology.

About Avutometinib (VS-6766)

Avutometinib is a RAF/MEK clamp that induces inactive complexes of MEK with ARAF, BRAF and CRAF potentially creating a more complete and durable anti-tumor response through maximal RAS pathway inhibition. Avutometinib is currently in late-stage development.

In contrast to other MEK inhibitors, avutometinib blocks both MEK kinase activity and the ability of RAF to phosphorylate MEK. This unique mechanism allows avutometinib to block MEK signaling without the compensatory activation of MEK that appears to limit the efficacy of other inhibitors. The U.S. Food and Drug Administration granted Breakthrough Therapy designation for the combination of Verastem Oncology’s investigational RAF/MEK clamp avutometinib, with defactinib, its FAK inhibitor, for the treatment of all patients with recurrent low-grade serous ovarian cancer (LGSOC) regardless of KRAS status after one or more prior lines of therapy, including platinum-based chemotherapy.

Verastem Oncology is currently conducting clinical trials with its RAF/MEK clamp avutometinib in RAS pathway-driven tumors as part of its (Raf And Mek Program). RAMP 201 is a registration-directed trial of avutometinib alone and in combination with defactinib in patients with recurrent LGSOC. Verastem Oncology has established clinical collaborations with Amgen and Mirati to evaluate LUMAKRAS (sotorasib) and KRAZATI (adagrasib) in combination with avutometinib in KRAS G12C mutant NSCLC as part of the RAMP 203 and RAMP 204 trials, respectively. Supported by the "Therapeutic Accelerator Award" Verastem Oncology received from PanCAN, the Company is conducting RAMP 205, a Phase 1b/2 clinical trial evaluating avutometinib and defactinib with gemcitabine/nab-paclitaxel in patients with front-line metastatic pancreatic cancer.

On July 5, 2023 OSE Immunotherapeutics SA (ISIN: FR0012127173; Mnemo: OSE) (Paris:OSE) reported that the trial’s Independent Drug Safety Monitoring Board (DSMB) provided a positive recommendation on the continuation until its completion of the Phase 2 clinical trial of IL-7 Receptor (IL-7R) antagonist Lusvertikimab (OSE-127) in ulcerative colitis (Press release, OSE Immunotherapeutics, JUL 5, 2023, View Source [SID1234633068]).

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In parallel, the European Medicines Agency (EMA) provided a positive opinion on Orphan Drug Designation for Lusvertikimab for the treatment of Acute Lymphoblastic Leukemia (ALL).

Nicolas Poirier, Chief Executive Officer of OSE Immunotherapeutics, comments: "After the planned DSMB review recommendation to continue the study until its completion, the Company’s primary and strategic focus remains clinical evaluation of Lusvertikimab in this ongoing ulcerative colitis Phase 2 study with end of accrual expected in the following months. In parallel, based on strong preclinical activity demonstrated by Lusvertikimab using patient’s leukemic samples, we are happy to have received a positive opinion on Orphan Drug Designation from the European Medicines Agency. Lusvertikimab orphan status for the treatment of Acute Lymphoblastic Leukemia from B or T cell precursors is opening future potential new indications in ALL, rare diseases with limited treatment options. We warmly thank our academic and clinician partners in Kiel, involved with us in this innovative research program."

ABOUT LUSVERTIKIMAB CLINICAL EVALUATION IN ULCERATIVE COLITIS (UC)

The ongoing Phase 2 clinical trial sponsored by OSE Immunotherapeutics is evaluating the efficacy and safety of Lusvertikimab (OSE-127) versus placebo in patients with moderate to severe active UC who failed or lost response or were intolerant to previous treatment(s) (CoTikiS trial: NCT04882007). A positive interim futility analysis was observed in the prespecified first 50 patients (i.e., 33% of the total patient enrollment in the study) having completed the induction phase. The upcoming major milestone for this Phase 2 clinical trial is expected in the following months with the top-line results after the induction phase (primary endpoint at week 10) and in H1 2024 for the first early assessment in maintenance after 6 months of therapy. UC is a debilitating and chronic inflammatory bowel disease which affects 3.3 million patients in US, Europe and Japan (1), representing 12.2 per 100,000 people by year (2). Despite broad available options, remission rates remain only 25-30% (3), leaving most patients without satisfactory treatments.

(1) EvaluatePharma
(2) Updated Incidence and Prevalence of Crohn’s Disease and Ulcerative Colitis in Olmsted County, Minnesota (1970-2011). Loftus EV et al. October 2014).
(3) Drugs Context. 2019; 8: 212572 –doi: 10.7573/dic.212572

ABOUT THE LUSVERTIKIMAB RESEARCH PROGRAM IN ACUTE LYMPHOBLASTIC LEUKEMIA (ALL)

This collaborative research program between OSE Immunotherapeutics and the University Medical Center Schleswig-Holstein in Kiel (Germany) evaluated the therapeutic potential of Lusvertikimab in targeting and blocking the high and dysregulated IL-7R expression observed in 84% of B- or T-Cell ALL (B- and T-ALL) patients. In particular, significant preclinical activity of Lusvertikimab has been demonstrated in models using leukemic samples from refractory and relapsed patients. The latest preclinical data on the use of Lusvertikimab for the treatment of B- and T-ALL and its dual anti-leukemic efficacy were presented and awarded at the American Society of Hematology (ASH) (Free ASH Whitepaper) annual meeting in December 2022.

In Europe, 7,000 cases of ALL are diagnosed each year (1). The condition is estimated to be affecting approximately 1.7 in 10,000 persons in the European Union (2). More globally, the number of diagnosed incident cases of ALL in Europe, US, Japan and China is estimated to achieve 26,482 cases in 2029(3).

(1) Gatta G, van der Zwan JM, Casali P, et al. Rare cancers are not so rare: The rare cancer burden in Europe. Eur. J. Cancer. 2011; 47: 2493-2511.
(2) Using epidemiological information from the European Cancer Information System (ECIS)(
(3) Global Data

ABOUT ORPHAN MEDICINAL PRODUCT DESIGNATION

Orphan designation in the European Union (EU) is granted by the European Commission after the opinion is issued by the EMA’s Committee for Orphan Medicinal Products (COMP). The EMA’s orphan designation is available to companies developing treatments for life-threatening or chronically debilitating conditions that affect fewer than five in 10,000 persons in the EU and for which no satisfactory method of diagnosis, prevention or treatment are authorized, or, if such exists, the medicine being developed must provide significant benefit. Medicines that meet the EMA’s orphan designation criteria qualify for financial and regulatory incentives that include protocol assistance from the EMA at reduced fees during the product development phase and access to centralized authorization procedure and a 10-year period of marketing exclusivity in the EU after product approval.

On July 5, 2023 Intensity Therapeutics, Inc. ("Intensity" or the "Company") (Nasdaq: INTS), a clinical-stage biotechnology company focused on the discovery and development of proprietary, novel immune-based intratumoral cancer therapies designed to kill tumors and increase immune system recognition of cancers, reported the closing of its upsized initial public offering of 3,900,000 shares of common stock at a public offering price of $5.00 per share (Press release, Intensity Therapeutics, JUL 5, 2023, View Source [SID1234633067]). In addition, Intensity has granted the underwriters a 45-day option to purchase an additional 585,000 shares of its common stock at the initial public offering price, less the underwriting discounts and commissions.

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In connection with the offering, the Company’s common stock began trading on The Nasdaq Capital Market on June 30, 2023, under the ticker symbol "INTS."

The net proceeds to Intensity from the offering (prior to any exercise of the underwriter’s over-allotment option), after deducting the underwriting discounts, commissions and transaction expenses were approximately $16.2 million.

The Benchmark Company and Freedom Capital Markets acted as the joint book-running managers for the offering.

The securities described above were being offered by the Company pursuant to a registration statement on Form S-1 (Registration No. 333-260565) that was previously filed with the U.S. Securities and Exchange (the "SEC") and declared effective on June 29, 2023. This offering was made only by means of a prospectus forming part of the effective registration statement. Copies of the final prospectus can be obtained through the SEC’s website at www.sec.gov or from: The Benchmark Company, LLC, Attention: Prospectus Department, 150 E. 58th Street, 17th floor, New York, NY 10155 at 212-312-6700 or by email at [email protected] and Freedom Capital Markets, 40 Wall Street, 58th Floor, New York, NY 10005, via email at [email protected] and via telephone at (800) 786-1469.

This press release shall not constitute an offer to sell or a solicitation of an offer to buy, nor shall there be any sale of these securities in any state or jurisdiction in which such offer, solicitation or sale would be unlawful.

On July 5, 2023 I-Mab (the "Company") (Nasdaq: IMAB), a clinical-stage biopharmaceutical company committed to the discovery, development, and commercialization of pioneering immunotherapies, reported the publication of a manuscript entitled "CLDN18.2 and 4-1BB bispecific antibody givastomig exerts antitumor activity through CLDN18.2-expressing tumor-directed T-cell activation" in the latest issue of The Journal for Immuno-Therapy of Cancer (JITC) (Press release, I-Mab Biopharma, JUL 5, 2023, View Source [SID1234633066]).

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Givastomig is engineered to bind to CLDN18.2-expressing cancer cells and co-stimulatory receptor 4-1BB on adjacent T cells, with the aim of activating T cells specifically within CLDN18.2-expressing tumors and triggering a potent tumor-killing effect. This innovative approach offers the potential for effective and targeted immuno-therapy in gastric cancer, a disease characterized by a poor prognosis and limited treatment options.

Results from this study demonstrated that 4-1BB+ T cells co-exist in close proximity to CLDN18.2+ gastric cancer cells in patients. Moreover, givastomig bound to tumor cells across a wide range of CLDN18.2 expression levels and induced 4-1BB activation only in the context of CLDN18.2 binding, indicating the targeted effect of 4-1BB activation in the presence of CLDN18.2+ cells. In the in vivo CLDN18.2-expressing tumor model, givastomig induces localized immune activation in tumors, increasing the ratio of CD8+/Treg cells, resulting in superior anti-tumor activity and long-lasting memory response against tumor rechallenge.

"The findings from our research demonstrate the significant potential of givastomig in treating gastric cancer patients with varying levels of CLDN18.2 expression," said Dr. Lin Shen, Professor of Clinical Oncology at the Beijing Cancer Hospital of Peking University, and Director of SIP LifeLink Oncology Research Institute. "By activating 4-1BB signaling in a CLDN18.2 engagement-dependent manner, givastomig can avoid the risk of liver toxicity and systemic immune response commonly observed with other 4-1BB stimulating agents in previous clinical trials."

"We are excited to see this manuscript published in JITC, as it showcases the innovative design and remarkable anti-tumor activity in preclinical models of givastomig," said Dr. Andrew Zhu, President of I-Mab. "This molecule has demonstrated promising results in this study by effectively activating T cells and triggering a localized immune response within the tumor microenvironment. With ongoing clinical studies, we aim to build upon these findings and ultimately make this innovative therapy accessible to patients with gastric cancer."

Givastomig is currently undergoing Phase 1 clinical studies both in the U.S. and in China. Encouragingly, the Phase 1 study has shown favorable safety profile and promising efficacy signals thus far. The Company intends to report additional clinical data from the study at a major medical conference in the second half of the year.

About Givastomig

Givastomig, also known as TJ-CD4B/ABL111, is a Claudin 18.2 and 4-1BB bispecific antibody capable of binding to tumor cells expressing Claudin 18.2, i.e., gastric cancer and pancreatic cancer cells, and stimulating intra-tumoral T cells by the 4-1BB arm designed to be activated only upon tumor engagement while silent elsewhere. Givastomig effectively maintains a strong tumor binding property and anti-tumor activity attributable to a synergistic effect of both Claudin 18.2 antibody and 4-1BB antibody while avoiding or minimizing liver toxicity and systemic immunotoxicity commonly seen with 4-1BB antibodies as a drug class. Being developed under collaboration between I-Mab and ABL Bio, a clinical-stage biotechnology company in South Korea, givastomig is currently being investigated in a phase 1 clinical study in the U.S. and China. In March 2022, the U.S. Food and Drug Administration (FDA) granted Orphan Drug Designation for givastomig for the treatment of gastric cancer, including cancer of gastroesophageal junction.

On July 5, 2023 CoImmune, Inc., a clinical stage immuno-oncology company working to redefine cancer treatment using best-in-class cellular immunotherapies, reported the publication of preclinical data demonstrating that a strategy based on the company’s proprietary Chimeric Antigen Receptor-Cytokine Induced Killer (CAR-CIK) cell platform provides advantages over single-targeting CARs including improved efficacy and high specificity in a model of acute myeloid leukemia (AML) (Press release, CoImmune, JUL 5, 2023, View Source [SID1234633065]). The preclinical data are published in Blood Advances, a peer-reviewed journal of the American Society of Hematology (ASH) (Free ASH Whitepaper).

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"CAR-engineered T-cells have demonstrated high therapeutic potential, but further development is required to ensure a safe and durable disease remission in AML," said Andrea Biondi, M.D., Professor of Pediatrics at the University of Milano-Bicocca and Scientific Director of the M. Tettamanti Research Center. "The impressive safety profile and encouraging activity of CAR-CIK cells is particularly attractive in the AML setting, in which older age and comorbidities hamper adoptive cell therapy options because of the risk of severe cytokine release syndrome or immune effector cell–associated neurotoxicity syndrome."

The publication, titled, "IL-3-zetakine combined with a CD33 costimulatory receptor as a dual CAR approach for safer and selective targeting of AML," describes an approach to developing CAR-CIK cells that co-express a first-generation low affinity anti-CD123 interleukin-3–zetakine (IL-3z) and an anti-CD33 as co-stimulatory receptor without activation signaling domains (CD33.CCR). The dual strategy demonstrated powerful antitumor efficacy against AML targets without any relevant toxicity on hematopoietic stem and progenitor cells (HSPCs) and endothelial cells. Specifically, the researchers found:

CD123 and/or CD33 knockout impairs leukemia growth by modulating multiple cancer pathways in a model of NPM1-mutated AML.
CAR-CIK cells mediate high antileukemic efficacy through transacting co-stimulation.
Low affinity CAR-CIK cells decrease on-target/off tumor toxicity against endothelial and HSPCs in vitro.
Low affinity CAR-CIK cells preserve antileukemic efficacy in vitro and improve antitumor control in vivo.
"CAR T-cell therapy in AML is limited by the absence of an ideal tumor-specific antigen," said Sarah Tettamanti, Ph.D., Tettamanti Center, Fondazione IRCCS San Gerardo dei Tintori, Monza, Italy. "In this study, we describe a novel strategy using CAR-CIK cells to target both CD33 and CD123 without the risk of severe on target/off-tumor toxicities. This approach has the potential to improve the outcome of patients with AML."