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Promontory Therapeutics to Present Data on PT-112 Mechanism of Action at the Society for Immunotherapy of Cancer’s 38th Annual Meeting

On October 26, 2023 Promontory Therapeutics Inc., a clinical stage biotech company advancing immunogenic small molecule approaches in oncology, reported that it will present a poster demonstrating the molecular mechanism of its lead therapeutic candidate, PT-112, at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper)’s (SITC) (Free SITC Whitepaper) 38th Annual Meeting (Press release, Promontory Therapeutics, OCT 26, 2023, View Source [SID1234636383]). SITC (Free SITC Whitepaper) is taking place November 1-5, 2023 in San Diego.

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PT-112 is the subject of ongoing Phase 2 clinical trials for metastatic castrate-resistant prostate cancer and thymic epithelial tumors, and a completed Phase 2a trial in non-small cell lung cancer.

Poster Session Details
Title: Molecular mechanisms of immunogenic cell death driven by PT-112
Abstract Number: 1106
Primary Category: Immune-Stimulants and Immune Modulators
Session Date/Time: Saturday, Nov. 4, 2023, 9:00 am – 8:30 pm PT
Session Location: Exhibit Halls A and B1 – San Diego Convention Center

For more information about Promontory Therapeutics and PT-112, visit www.PromontoryTx.com.

PharmaMar Group reports financial results to 30th September 2023

On October 26, 2023 PharmaMar (MSE:PHM) reported total revenues through September 30th, 2023 of €117.6 million, compared with €145.5 million in the same period last year (Press release, PharmaMar, OCT 26, 2023, View Source [SID1234636382]). Recurring revenues, which result from the sum of net sales plus royalties on sales made by our partners, totaled €98.3 million, compared to the €123.3 million reported for the first nine months of 2022. This change in revenues is mainly due to the introduction of two generic trabectedin products (Yondelis) on the European market, which has put significant pressure on prices. Thus, Yondelis reported net sales of €20.5 million through September 30th, 2023, compared with €52.2 million reported in the same period last year.

Revenues from Zepzelca (lurbinectedin) in Europe increased significantly. Revenues from the early access program in France, Austria and Spain grew to €26.1 million in the first nine months of the year, compared with €13.8 million in the first nine months of 2022. These revenues come mainly from France, although other early access programs are also open in countries such as Spain and Austria.

This increase is largely due to the positive adjustment made by the French authorities in relation to the previous year’s discounts. No further adjustments are expected for the year. The number of units demanded under this program has increased slightly compared to the same period of the previous fiscal year.

Included in recurring revenues is the sale of raw materials of both Yondelis and Zepzelca to our partners. This area reported revenues of €12.5 million through September 30th, 2023, compared with €17.8 million reported in the first nine months of the previous year.

It is important to highlight the growth in royalty revenues, which totaled €38.3 million through September 30th, representing an 8% increase over the same period last year. These revenues mainly include royalties received from our partner Jazz Pharmaceuticals for lurbinectedin sales in the U.S. which were €35.5 million vs. €32.9 million as of September 2022. The royalties recorded for the third quarter are an estimate, as information on sales made in that quarter by Jazz is not available at the date of publication of this report. Any discrepancies will be corrected in the following quarter.

In addition to the royalties received from Jazz Pharmaceuticals, royalties on Yondelis sales from our partners in the US and Japan totaled €2.8 million through September 30th of this year, €2.5 million for the same period of 2022.

With regard to non-recurring revenues mainly from licensing agreements, as of September 30th, these totaled €18.9 million compared with €22.1 million in the same period last year. During the first nine months of 2023 as well as 2022, revenues from this item came entirely from licensing agreements related to lurbinectedin. Through September 30th, 2023, R&D investment grew by 19% to €70 million.

Of the total R&D investment for the period, the oncology segment’s investment grew by 24% to €59.8 million and this increase is largely related to the confirmatory Phase III trial of lurbinectedin in Small-Cell Lung Cancer, known as LAGOON, which is progressing in patient recruitment. Part of this investment has also been earmarked for activities related to the start of another Phase IIb/III trial with lurbinectedin for the first-line treatment of leiomyosarcoma, which will commence shortly. The Company continues to invest in the clinical development of other molecules at earlier stages. A Phase II clinical trial is under way with ecubectedin in solid tumors, and Phase I clinical trials are also under way with ecubectedin, PM534 and PM54 for the treatment of solid tumors. Progress continues to be made in the preparation of new candidates for clinical development and in preclinical trials to bring new molecules into the clinical pipeline.

Despite the pressure on Yondelis sales prices and the growing R&D effort to develop new treatments, PharmaMar reported net income of €8.0 million through September 30th, 2023, compared with €43.4 million in the same period of the previous year.

As for the financial position to 30th September, PharmaMar Group had a cash and cash equivalents position of €185.5 million and total debt of €39.7 million, which translates into net cash of €145.9 million. This cash position includes expenditures already for dividend payments and the Company’s share buybacks.

PharmaMar Results Conference Call for Investors and Analysts

PharmaMar management will host a conference call and webcast for investors and analysts on Friday October 27th, 2023 at 13:00 (CET).

The numbers to connect to the teleconference are: +34 91 901 16 44 (from Spain), +1 646 664 1960 (from the US or Canada) or +44 20 3936 2999 (other countries). Participants’ access code: 892531. Interested parties can also follow the webcast live via the following link: View Source

A recording of the teleconference can be accessed on PharmaMar’s website by visiting the Events Calendar section of the Company’s website www.pharmamar.com

Oncternal Therapeutics Announces FDA Granted Fast Track Designation for ONCT-534 for the Treatment of Metastatic Castration-Resistant Prostate Cancer

On October 26, 2023 Oncternal Therapeutics, Inc. (Nasdaq: ONCT), a clinical-stage biopharmaceutical company focused on the development of novel oncology therapies, reported that the U.S. Food and Drug Administration (FDA) has designated ONCT-534, its novel dual-acting androgen receptor inhibitor (DAARI), as a Fast Track development program for the investigation of the treatment of patients with relapsed or refractory metastatic castration-resistant prostate cancer (mCRPC) resistant to approved androgen receptor pathway inhibitors (ARPIs) (Press release, Oncternal Therapeutics, OCT 26, 2023, View Source [SID1234636381]).

"The receipt of Fast Track designation for ONCT-534 supports our belief that patients with mCRPC who relapse after treatment with ARPIs such as enzalutamide or abiraterone, represent an important unmet medical need," said James Breitmeyer, M.D., Ph.D., Oncternal’s President and CEO. "We believe that due to ONCT-534’s novel mechanism of action, it may address important androgen receptor (AR) escape mechanisms that result in resistance to currently approved ARPIs. We look forward to working with FDA, investigators, and industry collaborators to bring ONCT-534 to patients as quickly as possible."

ONCT-534 interacts with both the N-terminal domain and the ligand-binding domain (LBD) of the AR, inhibiting cell growth and inducing AR degradation. Preclinical studies have shown activity in prostate cancer models against both unmutated AR, and against multiple mutations, including AR amplification, mutations in the AR LBD, and splice variants with loss of the AR LBD.

About Study ONCT-534-101
Study ONCT-534-101 is a Phase 1/2, single-arm, open-label, multi-center study to evaluate the safety and tolerability, pharmacokinetics, and preliminary anti-tumor activity of ONCT-534 in patients with mCRPC who have relapsed or are refractory to approved ARPIs including enzalutamide, abiraterone, apalutamide and daralutamide. After the safety and tolerability and preliminary antitumor activity of ONCT-534 have been assessed in Phase 1, Phase 2 will commence to further evaluate the safety and preliminary antitumor activity of ONCT-534 to allow for selecting an optimal dose.

Mustang Bio Announces FDA Acceptance of IND Application for MB-109, a Novel Combination of MB-101 (IL13Rα2‐targeted CAR-T cell therapy) and MB-108 (HSV-1 oncolytic virus), for the Treatment of Recurrent Glioblastoma and High-Grade Astrocytoma

On October 26, 2023 Mustang Bio, Inc. ("Mustang" or the "Company") (Nasdaq: MBIO), a clinical-stage biopharmaceutical company focused on translating today’s medical breakthroughs in cell and gene therapies into potential cures for difficult-to-treat cancers and rare genetic diseases, reported that the U.S. Food and Drug Administration ("FDA") has accepted the Company’s Investigational New Drug ("IND") application of MB-109 for the treatment of recurrent glioblastoma ("GBM") and high-grade astrocytoma (Press release, Mustang Bio, OCT 26, 2023, View Source [SID1234636380]). Mustang is planning to initiate a Phase 1 multicenter clinical trial at City of Hope ("COH") and the University of Alabama at Birmingham ("UAB") to assess the safety, tolerability and efficacy of MB-109, a novel combination of MB-101 (COH-developed IL13Rα2‐targeted CAR-T cell therapy) and MB-108 [Nationwide Children’s Hospital- ("Nationwide") developed HSV-1 oncolytic virus] in adult patients with recurrent GBM and high-grade astrocytomas that express IL13Rα2 on the surface of the tumor cells.

As previously reported, preclinical data presented at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) ("AACR") Annual Meeting in 2022 supported this combination therapy to potentially optimize results to treat recurrent GBM. The combination leverages MB-108 to reshape the tumor microenvironment ("TME") and make cold tumors "hot," thereby potentially improving the efficacy of MB-101 CAR-T cell therapy. Data presented separately on MB-101 and MB-108 showed that administration of these therapies was well tolerated in recurrent GBM patients. Two patients treated solely with MB-101 who had high levels of intratumoral CD3+ T cells pre-therapy (i.e., "hot" tumors) achieved complete responses lasting 7.5 and 31+ months, respectively. Importantly, of the 53 COH Phase 1 patients disclosed at AACR (Free AACR Whitepaper) in 2022, these 2 complete responses were observed in the 2 patients with the "hottest" tumors prior to treatment with MB-101. Phase 1 clinical trials of MB-101 at COH and of MB-108 at UAB continue to enroll patients.

Manuel Litchman, M.D., President and Chief Executive Officer of Mustang, said, "We are very pleased with the FDA’s acceptance of our IND application for MB-109, which allows Mustang to initiate a Phase 1 clinical trial to further evaluate combining MB-108 and MB-101, an attractive strategy for improving outcomes for patients with recurrent GBM and high-grade astrocytomas. Recurrent GBM remains a major challenge to treat, with a median overall survival rate of 6 months. We are committed to finding better treatment options for patients living with difficult-to-treat cancers and look forward to initiating our MB-109 Phase 1 clinical trial in 2024. The fact that this will be the first ever industry-sponsored trial to combine a CAR-T cell therapy with an oncolytic virus underscores Mustang’s commitment to innovation in the oncology and cell therapy space. Furthermore, FDA acceptance of our IND within 30 days of initial submission – despite the innovative aspect of the combination therapy and the complexity of the trial design – is testimony to the talent and resourcefulness of our team."

About MB-109 (MB-101 (IL-13Rα2 targeted CAR-T cells) + MB-108 oncolytic virus)

MB-109 is Mustang’s designation for the treatment regimen combining MB-101 (COH-developed IL13Rα2‐targeted CAR-T cell therapy) with MB-108 (Nationwide-developed HSV-1 oncolytic virus). The combination is designed to leverage MB-108 to make cold tumors "hot" and potentially improve the efficacy of MB-101 CAR-T cell therapy. MB-108 oncolytic virus is first injected to infect tumor cells which, in turn, leads to reshaping of the TME through recruitment of endogenous CD8- and CD3-positive effector T-cells. This inflamed TME potentially permits MB-101 CAR-T cells injected into and around the tumor to better infiltrate into and throughout the tumor mass, undergo activation and, ideally, effect tumor cell killing.

Molecular Partners Interim Management Statement Q3 2023: Continued Validation Seen Across the DARPin Portfolio

On October 26, 2023 Molecular Partners AG (SIX: MOLN; NASDAQ: MOLN), a clinical-stage biopharmaceutical company developing a class of custom-built protein drugs known as DARPin therapeutics ("Molecular Partners" or the "Company"), reported corporate highlights and unaudited financial results for the third quarter of 2023 (Press release, Molecular Partners, OCT 26, 2023, View Source [SID1234636379]).

"DARPin differentiation remains core to our strategy and we continue to develop programs where we see a distinct advantage to using our technology over others. In the second half of this year, we are making great progress towards our goal of showcasing DARPins’ potential to provide sophisticated solutions for patients living with cancers, by presenting updated results from MP0317 and initial data from our ongoing Phase 1 trial of MP0533 in relapsed/refractory AML later this year," said Patrick Amstutz, Ph.D., Molecular Partners’ Chief Executive Officer. "As our ongoing clinical trials remain on track, we are rapidly applying learnings from the positive data we have generated thus far from our Radio-DARPin Therapy platform to study new oncology targets in radiotherapy. The differentiated programs we are pursuing across our portfolio, in addition to our robust cash position, will serve as our springboard as we continue to execute on our clinical strategy in 2024."

Research & Development Highlights

Oncology

MP0533 (CD33 x CD123 x CD70 x CD3)

Recruitment in the MP0533 Phase 1/2a trial in patients with relapsed/refractory acute myeloid leukemia (AML) and myelodysplastic syndrome/AML (MDS/AML) is on track, with patients presently being treated at dose regimen five. Initial safety and activity data from this ongoing clinical trial will be presented at the American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting and Exposition in December 2023. Additional data are expected to be presented in H1 2024.

The clonal heterogeneity and lack of single AML-specific target antigens represent major challenges for the development of targeted immune therapies for AML. To overcome these hurdles, Molecular Partners designed MP0533, a novel tetraspecific T cell-engaging, half-life extended DARPin, which simultaneously targets CD33, CD123 and CD70, as well as CD3 on T cells. This unique mode of action is designed to enable avidity-driven, T cell-mediated killing of leukemic stem cells and malignant blast cells, which commonly co-express at least two of the three target antigens, while preserving a therapeutic window that minimizes damage to healthy cells.

MP0317 (FAP x CD40)

The Company has completed patient recruitment of the ongoing MP0317 dose escalation portion of the Phase 1 trial in patients with advanced solid tumors at the highest planned doses and will present latest results from this ongoing trial at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) Annual Meetings on November 3, 2023:

Abstract 721: Ongoing Phase 1 study of MP0317, a FAP-CD40 DARPin, shows a favorable safety profile and early evidence of tumor-localized CD40 activation in patients with advanced solid tumors

MP0317, a localized CD40 agonist, is designed to activate immune cells specifically within the tumor microenvironment by anchoring to fibroblast activation protein (FAP), which is highly expressed within tumors. This design is intended to reduce systemic toxicities seen historically with CD40 agonists by selectively directing CD40’s proven immuno-stimulatory properties to tumor tissues.

The data to be presented at SITC (Free SITC Whitepaper) build on the findings from the MP0317 Phase 1 trial previously presented at the Annual Meeting of the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) in June 2023, including data confirming tumor localized CD40 activation and indicating a favorable safety profile for MP0317. These data support planning of future combination studies of MP0317 with potential partners. Final data of this Phase 1 study are anticipated in H1 2024.

Radio-DARPin Therapy (RDT) platform

Molecular Partners’ RDT platform is being developed to provide a unique and innovative delivery system for radioactive payloads. Thanks to their small size as well as their high specificity and affinity, DARPins represent ideal vectors for efficient delivery of therapeutic radionuclides to solid tumors, while overcoming some historic limitations of radioligand therapy approaches.

The Company presented positive preclinical data from its RDT platform in September 2023 at the European Association of Nuclear Medicine (EANM) Annual Meeting, showing that DARPins can be engineered to increase tumor uptake as well as reduce accumulation in kidneys. Additional work is ongoing to demonstrate the ability of RDT to efficiently deliver high amounts of radioactivity for effective tumor eradication. Importantly, it was shown that many of the learnings for RDT are likely to be applicable across the platform, not merely to individual targets. More details on these efforts will be presented in 2024.

Molecular Partners continues to progress its RDT platform and portfolio of projects, both in-house and in partnership with Novartis, to translate and apply learnings across programs and targets. As previously announced, the tumor-associated protein Delta-like ligand 3 (DLL3) has been selected as one of the first targets of Molecular Partners’ proprietary RDT program.

Corporate and Management Highlights

Philippe Legenne, M.D., MBA, MHS, SVP Medical Strategy and Development, has assumed the role of acting Chief Medical Officer effective as of August 25, 2023, as previously announced. Dr. Legenne joined Molecular Partners in early 2020. During his tenure, he has led the clinical development strategy and execution across the Molecular Partners portfolio. Prior to joining Molecular Partners, Philippe held positions of increasing responsibility at Johnson & Johnson, GSK, and Novartis, both in the United States and Europe. In his most recent role prior to Molecular Partners, Philippe led the EU medical organization for the oncology portfolio at Amgen. He received his medical degree from the Université de Lille (France), an MBA from ESSEC Business School (Paris), and a Master’s degree in health economics from Université Paris Dauphine-PSL.

ESG

In its commitment to corporate sustainability, the Company is continuously refining its ESG strategy to align with the expansion of the pipeline, the future growth of the company and the values and principles of its employees and shareholders. Priority areas for the Company include corporate sustainability; human capital management and Diversity, Equity and Inclusion (DE&I); product service and safety; access to medicine; and business ethics. Elsewhere, Molecular Partners offers generous benefits spanning from health to retirement planning to its employees and fosters diversity and inclusion as a key element of its recruitment process.

Financial and Business Outlook
For the full year 2023, at constant exchange rates, the Company expects total expenses of CHF 65-70 million, of which approximately CHF 8 million will be non-cash effective costs for share-based payments, IFRS pension accounting and depreciation. This guidance does not include any potential receipts from R&D partnerships.

With CHF 207 million in cash and short-term time deposits and no debt as of September 30, 2023, the Company expects to be funded well into 2026, excluding any potential receipts from R&D partners.