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Philogen to attend Mediobanca 5th MidCap Conference on January 18, 2023 in Milan

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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Moleculin Granted FDA Fast Track Designation of WP1122 for the Treatment of Glioblastoma Multiforme

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.

"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.

INmune Bio, Inc. Reports Combination Therapy with INB03™ Overcomes Resistance to Trastuzumab-Deruxtecan in MUC4 expressing HER2+ Breast Cancer

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.

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.

iBio Announces Pricing of $3.5 Million Underwritten Public Offering

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.

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.

PERLA phase II trial of Jemperli (dostarlimab) plus chemotherapy shows positive results in first-line metastatic non-squamous non-small cell lung cancer

On December 7, 2022 GSK plc (LSE/NYSE: GSK) reported results from the PERLA phase II clinical trial investigating dostarlimab in combination with chemotherapy versus pembrolizumab in combination with chemotherapy as a first-line treatment for patients with metastatic non-squamous non-small cell lung cancer (NSCLC) (Press release, GlaxoSmithKline, DEC 7, 2022, View Source [SID1234624892]). Dostarlimab plus chemotherapy achieved very promising results for the primary endpoint of confirmed objective response rate (ORR) as well as for the key secondary endpoint of median progression-free survival (mPFS).

The PERLA phase II trial is a randomised, double-blind trial of 243 patients and is the largest global head-to-head trial of programmed death receptor-1 (PD-1) inhibitors in this patient population. The findings from the primary analysis were presented today at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Immuno-Oncology Congress 2022 in Geneva, Switzerland.

Hesham Abdullah, Senior Vice President, Global Head of Oncology Development, GSK said: "The head-to-head data from the PERLA trial showed that dostarlimab combined with chemotherapy provided robust anti-tumour activity in patients with previously untreated metastatic non-squamous non-small cell lung cancer. The positive results from this trial inform our future development plans and highlight the potential for dostarlimab to be our foundational immuno-oncology therapy as a single-agent and in combination with standards of care and novel therapies within our pipeline."

The primary endpoint was overall ORR by Response Evaluation Criteria in Solid Tumours (RECIST) as determined by blinded independent central review (BICR) and was 46% (n=56/121) in the dostarlimab treatment arm versus 37% (n=45/122) in the pembrolizumab treatment arm (difference in ORR: 9.32%; 80% CI: 1.46% to 17.18%).

The key secondary endpoint, mPFS, was 8.8 months (95% CI: 6.7 to 10.4) in the dostarlimab treatment arm versus 6.7 months (95% CI: 4.9 to 7.1) in the pembrolizumab treatment arm (HR 0.70 [95% CI: 0.50 to 0.98]).

The table below summarizes key results across all pre-specified programmed death ligand-1 (PD-L1) expression cohorts, as measured by Tumor Proportion Score (TPS).

ORR by RECIST (BICR)
(95% CI)

mPFS (Investigator Assessed)
(95% CI)
PFS HR
(95% CI)

Pre-specified PD-L1 expression cohorts measured by TPS

dostarlimab
+ chemo

pembrolizumab
+ chemo

dostarlimab
+ chemo
(CI)

pembrolizumab
+ chemo
(CI)

Overall
Population

46%
(37.2-55.6)

37%
(28.3-46.1)

8.8 months
(6.7-10.4)

6.7 months
(4.9-7.1)

HR 0.70
(0.50-0.98)

TPS < 1%

28%

33%

7.0 months
(4.9-9.7)

6.9 months
(4.7-9.6)

0.77
(0.46-1.28)

TPS ≥ 1%

59%

39%

10.4 months
(6.8-13.6)

6.1 months
(4.8-7.1)

0.66
(0.41-1.03)

TPS 1% to 49%

50%

34%

9.0 months
(5.3-NR)

5.4 months
(3.2-11.3)

0.67
(0.38-1.19)

TPS ≥ 50%

74%

48%

10.4 months
(5.8-NR)

6.7 months
(4.2-NR)

0.60
(0.27-1.29)

Treatment-emergent adverse events (TEAEs) for dostarlimab in the PERLA phase II trial were consistent with previous trials of similar regimens. The rate of TEAEs was 97% for both the dostarlimab and pembrolizumab treatments arms of the trial. The rate of Grade 3 or higher TEAEs was 59% in the dostarlimab treatment arm and 60% in the pembrolizumab treatment arm. The most common TEAEs were anaemia, asthenia, nausea, constipation, cough, dyspnoea, vomiting, decreased appetite, and neutropenia.

Solange Peters, M.D., Ph.D., Professor and Chair of Medical Oncology, University Hospital of Lausanne, Switzerland and ESMO (Free ESMO Whitepaper) President, said: "Understanding the role of immuno-oncology treatments in the NSCLC patient population is a significant goal we’re committed to in the oncology community. Despite advancements in treatment options, unmet need persists for health care providers and their patients. The data results presented at ESMO (Free ESMO Whitepaper)-IO add to the body of evidence of immuno-oncology agents such as dostarlimab and enhance our knowledge in this important area of research."

GSK is also studying dostarlimab in earlier lines of treatment for endometrial cancer and in combination with other therapeutic agents for patients with advanced/metastatic cancers. This research includes the recently announced positive headline RUBY Phase III trial results in patients with primary advanced or recurrent endometrial cancer, as well as the COSTAR Lung phase III trial comparing cobolimab, an investigational anti-TIM-3 targeting monoclonal antibody, plus dostarlimab plus docetaxel to dostarlimab plus docetaxel to docetaxel alone in patients with advanced NSCLC who have progressed on prior anti-PD-(L)1 therapy and chemotherapy.

About PERLA

The PERLA phase II trial is a global, randomised, double-blind trial of 243 patients evaluating the efficacy and safety of dostarlimab plus chemotherapy versus pembrolizumab plus chemotherapy in patients with metastatic non-squamous NSCLC without a known sensitising epidermal growth factor receptor, anaplastic lymphoma kinase, or receptor tyrosine kinase-1 mutation, V600E mutation of the BRAF gene or other genomic mutation for which an approved targeted therapy is available. The primary endpoint was objective response rate of dostarlimab plus chemotherapy versus pembrolizumab plus chemotherapy assessed by blinded independent central review per RECIST v1.1. Secondary endpoints include investigator-assessed progression-free survival per RECIST v1.1, overall survival, and safety.

About NSCLC

Lung cancer is one of the most commonly diagnosed cancers worldwide, with more than 2 million new cases diagnosed globally in 2020.1 It is the most common cause of cancer-related death in men and women worldwide, with relatively poor survival outcomes as evidenced by a five-year survival rate of 21%.2 Approximately 85% of lung cancer cases are NSCLC.3,4 NSCLC develops when once-healthy cells in the lungs begin to grow abnormally and form a tumour. When NSCLC spreads, or metastasizes, it can become more difficult treat, resulting in a significant need for new treatment approaches.

About Jemperli (dostarlimab)

Jemperli is a programmed death receptor-1 (PD-1)-blocking antibody that binds to the PD-1 receptor and blocks its interaction with the PD-1 ligands PD-L1 and PD-L2. Jemperli is being investigated in registrational enabling studies, as monotherapy and as part of combination regimens, including in women with recurrent or primary advanced endometrial cancer, women with stage III or IV non-mucinous epithelial ovarian cancer, and in patients with other advanced solid tumours or metastatic cancers. Jemperli is not approved anywhere in the world in combination with chemotherapy in first-line patients with metastatic non-squamous NSCLC or in combination with other agents to treat patients with advanced NSCLC who have progressed on prior anti-PD-L1 therapy and chemotherapy.

Jemperli was discovered by AnaptysBio and licensed to TESARO, Inc., under a Collaboration and Exclusive License Agreement signed in March 2014. The collaboration has resulted in three monospecific antibody therapies that have progressed into the clinic. These are: Jemperli (GSK4057190), a PD-1 antagonist; cobolimab, (GSK4069889), a TIM-3 antagonist; and GSK4074386, a LAG-3 antagonist. GSK is responsible for the ongoing research, development, commercialization, and manufacturing of each of these Products under the Agreement.

Important Information for Jemperli in the EU

Indication

Jemperli is indicated as monotherapy for the treatment of adult patients with mismatch repair deficient (dMMR)/microsatellite instability high (MSI H) recurrent or advanced endometrial cancer that has progressed on or following prior treatment with a platinum containing regimen.

Refer to the Jemperli Reference Information for a full list of adverse events and the complete important safety information in the EU.