On December 7, 2022 Replimune Group, Inc. (NASDAQ: REPL), a clinical stage biotechnology company pioneering the development of a novel class of tumor-directed oncolytic immunotherapies, reported that the Company has entered into a Master Clinical Trial Collaboration and Supply Agreement in relation to Replimune’s RP2/3 program in colorectal cancer (CRC) and hepatocellular carcinoma (HCC) (Press release, Replimune, DEC 7, 2022, View Source [SID1234624902]). Specifically, the companies will collaborate in third-line (3L) CRC and in first- and second-line (1L & 2L) HCC. Under the terms of the agreement, the companies will share costs and Roche will supply its currently approved drugs, atezolizumab and bevacizumab for 2L HCC and 3L CRC combined with RP3. Roche will also supply atezolizumab and bevacizumab for 1L HCC combined with RP3, and for 3L CRC combined with RP2. Approximately 30 patients will be enrolled within each cohort. Replimune will have responsibility for operationalizing the clinical trial.

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Atezolizumab in combination with bevacizumab is FDA approved and the current standard of care for the 1L treatment of unresectable HCC, with current treatment options for the treatment of 2L HCC being very limited. Combining RP3 with atezolizumab and bevacizumab has the potential to increase response rates and clinical benefit for patients with 1L disease, and to provide a much needed option for patients with 2L disease. While, bevacizumab is FDA approved to treat metastatic colorectal cancer, or mCRC, for first- or second-line treatment in combination with chemotherapy, late line CRC is a significant unmet need.

"This collaboration announcement is in keeping with our philosophy of partnering with industry leaders in oncology and in indications where our immunotherapies have the potential to become a key cornerstone of treatment," said Pamela Esposito, Ph.D., Chief Business Officer of Replimune. "With similar collaborations already in place for our lead candidate RP1 with Regeneron and Bristol-Myers Squibb, we believe this latest cost and supply sharing collaboration with Roche, a leader in GI cancers, will help us efficiently advance RP2/3 for the development of CRC and HCC."

Replimune remains on track to initiate its Phase 2 development program with RP2/3 in the first half of 2023. As previously announced, this program is intended to include Phase 2 clinical trials in squamous cell carcinoma of the head and neck (SCCHN; locally advanced and recurrent/metastatic), hepatocellular carcinoma (HCC; first line and second line) and colorectal cancer (CRC; third line), combined with current standard of care where appropriate.

About RP2 & RP3
RP2 and RP3 are enhanced potency oncolytic versions of HSV that express a fusogenic glycoprotein which provides robust immunogenic cell death together with additional immune-activating proteins. RP2 additionally expresses an anti-CTLA-4 antibody-like molecule and GM-CSF and RP3 additionally expresses the anti-CTLA-4 antibody-like molecule and the immune co-stimulatory pathway activating proteins CD40L and 4-1BBL. RP2 and RP3 are intended to provide targeted and potent delivery of these proteins to the sites of immune response initiation in the tumor and draining lymph nodes, with the goal of focusing systemic immune-based efficacy on tumors and limiting off-target toxicity.

On December 7, 2022 Replimune Group, Inc. (Nasdaq: REPL), a clinical stage biotechnology company pioneering the development of a novel class of tumor-directed oncolytic immunotherapies, reported a proposed public offering of $125 million of shares of its common stock and pre-funded warrants to purchase shares of common stock (Press release, Replimune, DEC 7, 2022, View Source [SID1234624901]). All securities in the offering will be offered by Replimune. In addition, Replimune intends to grant the underwriters a 30-day option to purchase up to an additional $18.75 million of shares of its common stock from Replimune at the public offering price, less the underwriting discounts and commissions.

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J.P. Morgan Securities LLC and SVB Securities LLC are acting as joint book-running managers for the proposed offering. The proposed offering is subject to market and other customary closing conditions, and Replimune cannot assure you as to whether or when the proposed offering may be completed.

The proposed offering will be made only by means of a preliminary prospectus supplement and the accompanying prospectus. A copy of the preliminary prospectus supplement and the accompanying prospectus relating to the proposed offering will be filed with the Securities and Exchange Commission (the "SEC") and may be obtained, when available, by visiting EDGAR on the SEC website at www.sec.gov. Alternatively, copies of the preliminary prospectus supplement and the accompanying prospectus, when available, may be obtained from J.P. Morgan Securities LLC, Attention: Broadridge Financial Solutions, 1155 Long Island Avenue, Edgewood, NY 11717, by telephone at (866) 803-9204, or by e-mail at [email protected]; or SVB Securities LLC, Attention: Syndicate Department, 53 State Street, 40th Floor, Boston, MA 02109, by telephone at 1-800-808-7525, ext. 6105, or by email at [email protected]. The final terms of the proposed offering will be disclosed in a final prospectus supplement to be filed with the SEC.

The securities described above are being offered by Replimune pursuant to its shelf registration statement on Form S-3, including a base prospectus, that was previously filed by Replimune with the SEC on June 23, 2022 and declared effective by the SEC on July 27, 2022. This press release shall not constitute an offer to sell or the solicitation of an offer to buy, nor shall there be any sale of securities, in any state or jurisdiction in which such an offer, solicitation or sale would be unlawful prior to registration or qualification under the securities laws of any such state or jurisdiction.

On December 7, 2022 Vor Bio (Nasdaq: VOR), a clinical-stage cell and genome engineering company, reported that initial clinical data from VBP101, its Phase 1/2a multicenter, open-label, first-in-human study of tremtelectogene empogeditemcel or "trem-cel" (formerly VOR33) in patients with acute myeloid leukemia (AML) (Press release, PureTech Health, DEC 7, 2022, View Source [SID1234624899]). The data observed from the first treated patient support the potential of a trem-cel transplant to be successfully manufactured, to engraft normally, and to maintain blood counts following treatment with the CD33-targeted therapy Mylotarg. The clinical trial continues to enroll patients and additional data are expected in 2023.

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"These early engraftment data represent the first time genome engineering has been used to genetically alter donor cells by removing an antigen present on blood cells, thereby allowing treatment using a CD33 targeted therapy while protecting normal blood cells," said Dr. Robert Ang, Vor Bio’s President and Chief Executive Officer. "These encouraging data represent the first clinical validation of our platform to potentially enable next-generation transplants for patients with blood cancers. We look forward to sharing additional data updates in 2023."

Trem-cel Displayed Normal Engraftment

A product dose of 7.6 x106 CD34+ viable cells/kg, with a CD33 editing efficiency of 88% was manufactured. Following myeloablative conditioning, trem-cel was infused with no infusion reactions. The patient achieved neutrophil engraftment 10 days post-transplant which was within expectations for CD34-enriched transplants. Platelet recovery was observed on Day 22. Hematopoietic cell sub-population reconstitution was robust with over 90% of peripheral blood cells negative for CD33 expression, and 100% donor chimerism was achieved. These data provide proof-of-concept that trem-cel can engraft as expected and that CD33 does not appear to be biologically necessary for engraftment and hematopoietic reconstitution.

Mylotarg Tolerated at Initial Dose Level

The patient received Mylotarg at a dose of 0.5 mg/m2. At this dose, Mylotarg saturates CD33 antigen in patients with relapsed/refractory AML1, and in the original Phase 1 trial of Mylotarg2, neutropenia was observed across dose levels starting at 0.25mg/m2 within 14 days of infusion. No treatment related adverse events and no liver enzyme changes were observed through day 20 following Mylotarg dosing. No negative impacts to neutrophil and platelet counts were observed through day 20, suggesting tolerability at this initial dose level.

"The unmet medical need for AML is significant and hematopoietic cell transplant is the best hope for these patients," said Brenda Cooper, M.D., Professor of Medicine in the Cellar Therapy Program at University Hospitals, Seidman Cancer Center, and an investigator in the VBP101 study. "Early treatment data in the first patient show that trem-cel can engraft normally and maintain normal hematopoiesis following Mylotarg dosing, which typically causes severe cytopenias. These data support the promise of this approach."

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1Mylotarg ODAC 2017
2Sievers 1999 Blood 93:3678

Conference Call & Webcast Information
Members of the Vor Bio management team, joined by Dr. Brenda Cooper, will conduct a live conference call and webcast today at 8:00 am Eastern Time.

Listeners can register for the webcast via this link.

Analysts wishing to participate in the Q&A session should use this link.

A replay of the webcast will be available via the investor section of the Company’s website at www.vorbio.com approximately two hours after the call’s conclusion.

About AML

AML is the most common type of acute leukemia in adults and one of the deadliest and most aggressive blood cancers, affecting 20,000 newly diagnosed patients each year in the United States. Approximately half of patients with AML who receive a hematopoietic cell transplant (HCT) suffer a relapse of their leukemia, with two-year survival rates of less than 20%, and relapse rates are higher for patients with certain adverse risk features. The fragility of engrafted hematopoietic stem cells prevents treatment following transplant, giving the cancer a chance to return.

About the VBP101 Clinical Trial

VBP101 is a Phase 1/2a, multicenter, open-label, first-in-human study of trem-cel in participants with AML who are undergoing human leukocyte antigen (HLA)-matched allogeneic hematopoietic cell transplant (HCT). Trem-cel is an allogeneic CRISPR/Cas9 genome-edited hematopoietic stem and progenitor cell (HSPC) therapy product, lacking the CD33 protein. It is being investigated for participants with CD33+ AML at high risk for relapse after HCT to allow post-HCT targeting of residual CD33+ acute AML cells using Mylotarg without toxicity to engrafted cells. Participants undergo a myeloablative HCT with matched related or unrelated donor CD34-selected HSPCs engineered to remove CD33 expression (trem-cel drug product). Mylotarg is given after engraftment for up to four cycles. The primary endpoint is the incidence of successful engraftment, defined as the first day of 3 consecutive days of absolute neutrophil count (ANC) 500 cells/mm2 by day 28. Part 1 of this study is evaluating the safety of escalating Mylotarg dose levels to determine the maximum tolerated dose (MTD) and recommended Phase 2 dose. Part 2 will expand the number of participants to evaluate the Mylotarg recommended Phase 2 dose. For more information, visit: View Source

About Trem-cel

Tremtelectogene empogeditemcel (trem-cel), formerly VOR33, is a genome-edited hematopoietic stem and progenitor allogeneic donor product candidate where CD33 has been deleted using genome engineering. Transplant with trem-cel is designed to replace standard of care transplants for patients suffering from AML and potentially other blood cancers. Trem-cel has the potential to enable powerful targeted therapies in the post-transplant setting including CD33-targeted CAR-T cells.

On December 7, 2022 Philogen reported its attendance at the 5th MidCap Conference organised by Mediobanca (Press release, Philogen, DEC 7, 2022, View Source [SID1234624898]).

Prof. Dario Neri (CEO and CSO), Laura Baldi (CFO), and Emanuele Puca (Investor Relations) will participate at the event. The objective of the MidCap Conference is to bring the financial community together with the most deserving MidCap companies listed on the Italian Stock Exchange.

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On December 7, 2022 Moleculin Biotech, Inc., (Nasdaq: MBRX) ("Moleculin" or the "Company"), a clinical stage pharmaceutical company with a broad portfolio of drug candidates targeting highly resistant tumors and viruses, reported that the U.S. Food and Drug Administration ("FDA") has granted Fast Track designation of WP1122 for the treatment of Glioblastoma Multiforme ("GBM"). The FDA’s Fast Track designation is intended to potentially facilitate the development and expedite the review of novel therapies to treat serious conditions for which there is unmet medical need (Press release, Moleculin, DEC 7, 2022, View Source [SID1234624897]). With the Fast Track designation, Moleculin is potentially eligible for more frequent regulatory meetings and communications with the FDA.

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"We believe receiving Fast Track designation validates the serious unmet medical need for the treatment of GBM, the most aggressive form of malignant primary brain cancer," commented Walter Klemp, Chairman and Chief Executive Officer of Moleculin. "We believe that based on the promising animal model data that supports GBM as one of many potential indications, the clearance of our IND for WP1122 in GBM, and Orphan Drug Designation previously received from the FDA, WP1122 is well-positioned to be a potential treatment option for this devastating disease."

GBM is the most aggressive malignant primary brain tumor and remains as an incurable tumor with a median survival of only 15 months.1 It is the most common malignant primary brain tumor making up 54% of all gliomas and 16% of all primary brain tumors,2 and despite advancements, survival rates for patients with GBM have shown no notable improvement in population statistics in the last three decades.3 The average annual age-adjusted incidence rate of GBM is 3.19 per 100,000 persons in the United States.4

WP1122 was developed as a 2-DG prodrug to provide a more favorable pharmacological profile and was found to have greater potency than 2-DG alone in preclinical models where tumor cells require higher glycolytic activity than normal cells. Although activity in animals does not necessarily translate to humans, preclinical studies in mice transplanted with human brain tumors showed that WP1122 outperformed the standard of care, temozolomide, and performed even better in combination with temozolomide.

In September of 2022, Moleculin was granted Orphan Drug Designation of WP1122 for the treatment of GBM from the FDA. Additionally, based on preclinical data indicating the potential for WP1122 as a treatment for GBM, Moleculin received FDA clearance of its Investigational New Drug application to initiate a Phase 1 open label, single arm, dose escalation study of the safety, pharmacokinetics and efficacy of oral WP1122 in adult patients with GBM. The Company is currently evaluating opportunities for collaboration in clinical development.