On October 26, 2023 PTC Therapeutics, Inc., (NASDAQ: PTCT) reported a corporate update and financial results for the third quarter ending September 30, 2023 (Press release, PTC Therapeutics, OCT 26, 2023, View Source [SID1234636384]).

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"I am very proud of the progress all of our teams made this quarter," said Matthew Klein, M.D., Chief Executive Officer, PTC Therapeutics, Inc. "The recent Royalty Pharma transaction and restructuring initiatives that we implemented have put the company on a strong financial footing. We believe we are well positioned to deliver on our most promising opportunities for growth, including the potential sepiapterin revenue opportunity of more than $1 billion and the PTC518 HD program."

Key Corporate Updates:

● Finalized strategic partnership transaction with Royalty Pharma, in which Royalty Pharma acquired additional royalties of Evrysdi for $1.0 billion upfront. The agreement included options for PTC to sell the remainder of its royalties of Evrysdi for up to $500 million or for Royalty Pharma to acquire half of such retained royalties for up to $250 million at a later date, less royalties received by PTC. PTC maintains all economics associated with up to $250 million in the remaining commercial sales milestones associated with Evrysdi global net sales.
● Third quarter 2023 revenue for the DMD franchise was $136 million, supporting increasing 2023 DMD franchise revenue guidance to between $565 million and $595 million.
oTranslarna (ataluren) quarterly net product revenue was $69 million, with new patients in existing geographies and continued geographic expansion.
oEmflaza (deflazacort) quarterly net product revenue was $67 million, with new patient starts and high compliance.

Key Clinical and Regulatory Updates:

● For Translarna, following the negative opinion from the CHMP, the CHMP gave PTC the option to request re-examination of both opinions or only one opinion. PTC decided to pursue re-examination of the negative opinion on renewal of the conditional authorization only. In accordance with EMA guidelines, PTC expects the opinion from the re-examination procedure in late January 2024, with ratification of that opinion by the European Commission 67 days later.
● For the United States, a type C meeting with the FDA for Translarna is scheduled for the fourth quarter of 2023.
● PTC held a pre-NDA meeting in the third quarter with the FDA for sepiapterin in PKU to discuss the NDA submission. At the meeting, the FDA stated that the sepiapterin clinical safety and efficacy data supported NDA submission for the treatment of pediatric and adult PKU patients. It was requested that PTC complete an additional 26-week nonclinical mouse study to assess sepiapterin carcinogenicity potential prior to NDA submission. This nonclinical study was not initially required when sepiapterin was acquired from Censa, as the NDA submission was planned under the Section
505(b)(2) pathway. With PTC’s decision to file under the Section 505(b)(1) pathway, the 26-week study is considered a required NDA component needed to inform labeling and is typically completed prior to submission. PTC will continue to discuss with the FDA the potential to submit the mouse study results during the NDA review process. PTC now expects the NDA submission to occur no later than the third quarter of 2024; the submission could be submitted during the second quarter of 2024 if the nonclinical study report can be submitted during the review process.
● PTC expects to submit an MAA to the EMA for sepiapterin for the treatment of PKU in the first half of 2024.
● Enrollment in the PIVOT-HD study for PTC518 for Huntington’s disease continues outside of the US for both the stage 2 and early stage 3 cohorts. PTC expects the next data update to occur in the first half of 2024. This update will include 12-month data on the initial group of subjects for which data was reported in June of this year.
● PTC had a type A meeting with the FDA to discuss the clinical safety data needed to enable enrollment of the PIVOT-HD trial at US study sites. At the meeting, the FDA stated that the existing three months of safety data could support 12-week dosing at 5mg and 10mg dose levels and that six months of clinical safety data demonstrating a similar favorable safety profile could support 12-month dosing in PIVOT-HD.
● PTC had a type C written-response-only meeting with FDA for vatiquinone for Friedreich ataxia to determine whether the data from the MOVE-FA study would be sufficient to support an NDA for accelerated approval. In their written response, the FDA stated that while they see the value of upright stability as a clinically meaningful endpoint, they believed a confirmatory study would likely be needed to support NDA submission. PTC has requested a follow-up live meeting to address the issues raised by the FDA.
● PTC is participating in a scientific advice procedure with the EMA to determine if the MOVE-FA data could support a conditional marketing authorization application in the EEA. PTC expects to have the outcome of this procedure in the first quarter of 2024.
● PTC had an informal meeting with the FDA for Upstaza for AADC deficiency. The FDA stated that the data PTC has provided to support comparability between the clinical drug product and the intended commercial drug product were still not sufficient. The FDA did say that the available data from the ongoing clinical study in the US assessing the safety of the drug delivery cannula could be used to support a BLA for accelerated approval based on biomarker data demonstrating a treatment-related increase in de novo dopamine production. The FDA suggested that PTC conduct a pre-BLA meeting prior to BLA submission to review BLA contents. This meeting has been scheduled for December 2023, and pending the outcome, PTC expects to submit the BLA shortly thereafter.

Third Quarter 2023 Financial Highlights:

● Total revenues were $196.6 million for the third quarter of 2023, compared to $217.1 million for the third quarter of 2022.
● Total revenues include net product revenue across the commercial portfolio of $144.0 million for the third quarter of 2023, compared to $134.2 million for the third quarter of 2022. Total revenues also include collaboration, royalty and manufacturing revenue of $52.5 million in the third quarter of 2023, compared to $82.9 million for the third quarter of 2022.
● Translarna net product revenue was $69.0 million for the third quarter of 2023, compared to $76.6 million for the third quarter of 2022. These results were due to new patients in existing geographies and continued geographic expansion, while the quarter over quarter decrease was due to the timing of bulk government orders.
● Emflaza net product revenue was $67.4 million for the third quarter of 2023, compared to $54.8 million for the third quarter of 2022. These results reflect new patient starts and high compliance.
● Roche reported Evrysdi 2023 year-to-date sales of approximately CHF 1,065 million, resulting in royalty revenue of $50.2 million to PTC for the third quarter of 2023, as compared to $32.9 million for the third quarter of 2022.
● Based on U.S. GAAP (Generally Accepted Accounting Principles), GAAP R&D expenses were $164.2 million for the third quarter of 2023, compared to $165.5 million for the third quarter of 2022.
● Non-GAAP R&D expenses were $150.2 million for the third quarter of 2023, excluding $14.0 million in non-cash, stock-based compensation expense, compared to $150.4 million for the third quarter of 2022, excluding $15.1 million in non-cash, stock-based compensation expense.
● GAAP SG&A expenses were $80.9 million for the third quarter of 2023, compared to $80.1 million for the third quarter of 2022.
● Non-GAAP SG&A expenses were $67.9 million for the third quarter of 2023, excluding $13.0 million in non-cash, stock-based compensation expense, compared to $66.5 million for the third quarter of 2022, excluding $13.6 million in non-cash, stock-based compensation expense.
● During the third quarter of 2023, PTC incurred additional reductions in workforce as part of the continued strategic portfolio prioritization, which resulted in a one-time charge of approximately $22.6 million recorded to R&D and SG&A expense.
● The change in the fair value of deferred and contingent consideration was a loss of $1.5 million for the third quarter of 2023, compared to a gain of $5.3 million for the third quarter of 2022.
● The net loss was $133.0 million for the third quarter of 2023, compared to a net loss of $109.3 million for the third quarter of 2022.
● Cash, cash equivalents, and marketable securities was $294.8 million on September 30, 2023, compared to $410.7 million at December 31, 2022.
● Shares issued and outstanding as of September 30, 2023, were 75,459,022.

PTC Updates Full Year 2023 Financial Guidance as Follows:

● PTC anticipates total revenues for full-year 2023 to be between $940 million and $1.0 billion.
● PTC anticipates net product revenue for the DMD franchise for full-year 2023 to be between $565 million and $595 million.
● PTC anticipates GAAP R&D and SG&A expenses for full-year 2023 to be between $915 million and $965 million.
● PTC anticipates Non-GAAP R&D and SG&A expenses for full year 2023 to be between $810 million and $860 million, excluding estimated non-cash stock-based compensation expense of $105 million.
● PTC expects to incur $37 million of one-time expenses related to the achievement of clinical success-based milestones from previous acquisitions and expenses associated with a rights exchange agreement, which have already been paid in equity and cash.

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.

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.

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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

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]).

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"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.

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.

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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.