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.

On December 6, 2022 INmune Bio, Inc. (NASDAQ: INMB) (the "Company"), a clinical-stage immunology company focused on developing treatments that harness the patient’s innate immune system to fight disease, reported it has been invited to present data on the combination of INB03 and trastuzumab-deruxtecan (TDxd) for treatment of HER2 positive breast cancer (Press release, INmune Bio, DEC 7, 2022, View Source [SID1234624896]). The data suggests INB03, a dominant-negative TNF inhibitor that selectively sequesters soluble TNF (sTNF), may provide a novel mechanism for reversing resistance to HER2 targeted immunotherapy, and through this mechanism, may further enhance efficacy and reduce toxicity associated with TDxd treatment in some patients. TDxd is a trastuzumab-based antibody drug conjugate used to treat certain patients with HER2 breast cancer.

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Mucin 4 (MUC4), an easily measured glycoprotein on the cell surface of some HER2 positive breast cancer, is a biomarker of resistance to immunotherapy, including trastuzumab, and is also a biomarker of poor survival in women with HER2+ breast cancer. Expression of MUC4 is believed to be driven by soluble TNF produced by breast cancer cells. MUC4 is at the root of therapy resistance as it causes steric hinderance and prevents binding of trastuzumab to HER2 receptors and further promotes an immunosuppressive tumor microenvironment (TME). Dr. Schillaci has previously shown that INB03 downregulates MUC4 and reverses resistance to trastuzumab in MUC4 expressing HER2+ breast cancers. Prior to this data, it was not known if MUC4 expression by HER2 positive breast cancer has an impact on response to TDxd.

Using the well-established nude mouse model of HER2 resistance in mice with MUC4 expressing HER2+ breast cancer, JIMT-1 tumors exhibit decreased growth when treated with TDxd. The combination of TDxd with INB03 improved anti-tumor immunology of the TME with fewer myeloid derived suppressor cells (MDSC) and more antitumor tumor macrophages, which further decreased tumor growth compared to TDxd alone. Importantly, the addition of INB03 did not increase the toxicity of TDxd in these animals.

"Our data in a trastuzumab multi-resistant model of HER2 positive breast cancer shows that the resistance mechanisms observed with trastuzumab immunotherapy persist with trastuzumab-deruxtecan treatment," said Dr. Roxana Schillaci of Instituto de Biología y Medicina Experimental in Buenos Aires. "However, neutralizing soluble TNF with INB03 overcomes these resistance mechanisms and may promote an improved response to TDxd in women with trastuzumab-resistant disease, and may further provide opportunity for treatment with other types of immunotherapy."

% tumor growth inhibition of JIMT-1 tumor by volume No TDxd TDxd 1.25mg TDxd 2.5mg TDxd 5.0mg
no INB03 0 % 37 % 61 % 81 %
plus INB03 0 % 73 % 81 % 98 %
Increased antitumor effect with combination therapy NA 97 % 33 % 21 %

Poster ID: P1-11-12
Poster Title: Soluble TNFα blockade enhances trastuzumab deruxtecan antitumor effect in HER2-positive breast cancer
Date: Tuesday December 6, 2022
Time: 5:00 PM – 6:15 PM

"Trastuzumab-deruxtecan has revolutionized the treatment of women with HER2+ breast cancer, but 50% of women who receive the therapy for metastatic disease progress after two years," said RJ Tesi, MD, CEO of INmune Bio. "MUC4 expression is an easily determined biomarker that predicts resistance to trastuzumab based immunotherapy. Adding INB03 reverses the resistance mechanisms and may improve response to therapy, opening the door to treatment with other immunotherapies and may offer an opportunity to decrease toxicity of those immunotherapies in these patients," concluded Dr. Schillaci.

About INB03

INB03 is a Dominant Negative Tumor Necrosis Factor (DN-TNF) inhibitor that neutralizes soluble TNF (sTNF) without affecting trans membrane TNF (tmTNF) or TNF receptors. Compared to currently available non-selective TNF inhibitors, INB03 preserves the immune response to cancer by decreasing immunosuppressive cells in the TME including TAM and MDSC while promoting recruitment of anti-tumor immune cells including cytolytic CD8+ lymphocytes, NK cells and anti-tumor macrophages. INB03 has completed an open label dose-escalation Phase I trial in patients with advanced cancer. In that trial, INB03 was found to be safe and well tolerated – no dose limiting toxicity was found. INB03 decreased blood biomarkers of inflammation in patients with advanced cancer. INmune is seeking non-dilutive funding and/or a partnership to fund a Phase II trial that uses INB03 as part of combination therapy.

On December 6, 2022 iBio, Inc. (NYSEA: IBIO) ("iBio" or the "Company"), an AI-driven innovator of precision antibody immunotherapies, reported the pricing of its previously announced underwritten public offering of an aggregate of 3,365,385 shares of its common stock (or pre-funded warrants in lieu thereof), Series A warrants to purchase up to 3,365,385 shares of common stock and Series B warrants to purchase up to 3,365,385 shares of common stock, at a combined public offering price of $1.04 per share (or pre-funded warrants in lieu thereof) and accompanying warrants (Press release, iBioPharma, DEC 7, 2022, View Source [SID1234624895]). The Series A warrants will have an exercise price of $1.04 per share, will be exercisable immediately upon issuance and will expire five years from the date of issuance, and the Series B warrants will have an exercise price of $1.04 per share, will be exercisable immediately upon issuance and will expire twenty-four months from the date of issuance. The closing of the offering is expected to occur on or about December 9, 2022, subject to the satisfaction of customary closing conditions.

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In connection with the offering, the Company has granted the underwriter a 30-day option to purchase 504,807 additional shares of its common stock and/or warrants to purchase up to 1,009,614 additional shares of its common stock at the public offering price, less underwriting discounts and commissions.

H.C. Wainwright & Co. is acting as sole book-running manager for the public offering.

The gross proceeds from the offering, before deducting the underwriting discounts and commissions and other offering expenses, are expected to be approximately $3.5 million. The Company intends to use the net proceeds from the offering primarily for operating costs, including for research and development and other trial preparation expenses in addition to working capital needs and for other general corporate purposes, which may include retention and severance payments to certain of our employees or former employees and principal payments pursuant to the terms of its amended Credit Agreement.

The securities described above are being offered by iBio pursuant to a shelf registration statement on Form S-3 (File No. 333-250973) that was previously filed with the Securities and Exchange Commission (the "SEC") on November 25, 2020 and became effective on December 7, 2020. The securities are being offered only by means of a prospectus, including a prospectus supplement, forming a part of the effective registration statement. A preliminary prospectus supplement and accompanying base prospectus relating to, and describing the terms of, the offering has been filed with the SEC and is available on the SEC’s website at www.sec.gov. When available, electronic copies of the final prospectus supplement and the accompanying base prospectus may be obtained on the SEC’s website at www.sec.gov and may also be obtained by contacting H.C. Wainwright & Co., LLC at 430 Park Ave., New York, New York 10022, by telephone at (212) 856-5711, or by email at [email protected].

This press release does not constitute an offer to sell or a solicitation of an offer to buy the securities in this offering, nor shall there be any sale of these securities in any state or other jurisdiction in which such offer, solicitation or sale would be unlawful prior to the registration or qualification under the securities laws of any such state or other jurisdiction.