On August 9, 2023 Photocure ASA (OSE: PHO) reported Hexvix/Cysview revenues of NOK 115.9 million in the second quarter of 2023 (Q2 2022: NOK 99.9 million), and an EBITDA of NOK 23.4 million (NOK 1.4 million). The Company reiterates its 2023 annual guidance of new Saphira blue light tower installations in the U.S. expected in the range of 65 to 75, anticipated consolidated product revenue growth above 20%, and positive EBITDA excluding business development spending (Press release, PhotoCure, AUG 9, 2023, View Source [SID1234634106]).

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"In the second quarter of 2023, Hexvix/Cysview revenue increased 16% year over year driven by higher unit sales in the U.S., price increases and foreign exchange. We generated over NOK 23 million in EBITDA, including a positive contribution from our commercial business and a milestone payment from Asieris related to the clinical development of Cevira. During the second quarter, we delivered 4% sequential unit sales growth in North America and 6% in Europe, demonstrating continued positive traction in the region," says Dan Schneider, President & Chief Executive Officer of Photocure.

Photocure reported total group revenues of NOK 144.3 million in the second quarter of 2023 (NOK 100.6 million), and an EBITDA* of NOK 23.4 million (NOK 1.4 million). Hexvix/Cysview revenues ended at NOK 115.9 million in the quarter (Q2 2022: NOK 99.9 million), and the total group revenues includes a milestone payment related to the development of Cevira by Asieris of NOK 26.9 million. The EBIT was NOK 16.8 million (NOK -4.6 million), and the cash balance at the end of the period was NOK 258.9 million. Photocure paid off the balance of its term debt during the second quarter of 2023.

At the end of the second quarter of 2023, the total installed base of rigid blue light cystoscopes (BLC) in the U.S. was 327, an increase of 21% or 56 towers since the same period in 2022. These figures do not include the 69 flexible cystoscopy towers that were installed in the U.S. as of December 31, 2022. In early 2023, Karl Storz announced that it will no longer sell flexible BLC equipment for use in the surveillance setting and will cease servicing existing units when the availability of replacement parts has been exhausted, anticipated in late 2023. Despite Karl Storz’ decision to discontinue its flexible BLC equipment, surveillance of bladder cancer patients with flexible BLC remains a strategic priority for Photocure, and the Company plans to pursue initiatives to restore this specialized equipment in the U.S. and in international markets.

"Offsetting the loss in flexible BLC equipment, the installed base of rigid blue light capital equipment expanded once again, with 13 new Saphira towers installed in Q2. Eight new placements and five upgrades were installed prior to Karl Storz’s recent promotional discount program which went into effect in July and shifted the timing of some tower installations into the third quarter. In July alone, 40 quotes were issued for new Saphira systems, and so far in Q3, 12 purchase orders have been received. We believe that this momentum will result in a strong second half of the year for new tower placements," Schneider adds.

Photocure reiterates its guidance for 2023 and continues to expect new Saphira blue light tower installations in the range of 65 to 75, consolidated product revenue growth above 20%, and positive EBITDA excluding business development spending.

"I remain confident in Photocure’s future and our ability to bring Hexvix/Cysview to more patients and establish Blue Light Cystoscopy as standard of care. The new technology cycle of high-definition blue light equipment from multiple manufacturers is expected to significantly increase the use of Hexvix/Cysview. We continue to await information from Karl Storz and the FDA regarding the Citizen’s Petition to re-classify BLC as a Class 2 device, which we believe will enable additional equipment manufacturers to enter the U.S. market and build critical mass behind BLC. Given our prior success in creating and accelerating the use of BLC in the large untapped bladder cancer surveillance market, we are pursuing a strategy to reintroduce the technology in the near to intermediate future. For the remainder of the year, we will focus on driving sales in the rigid cystoscopy setting, and we look forward to several milestone events including the anticipated Phase 3 results for Hexvix in China and Cevira with our partner Asieris," Schneider concludes.

Photocure also announced today that Jan H. Egberts, M.D. has decided to step down from his position as Chairperson of the Company’s Board of Directors due to increased time commitments to his personal companies. Dr. Egberts will leave the Board in September 2023, and the Nomination Committee has initiated a search for a new Chairperson.

Robert Blatt, Chair of Photocure’s Nomination Committee, said, "I would like to express my gratitude to Jan, who has made important contributions to Photocure during his more than six years as Chairperson of the Board. His dedication and medical experience will be missed".

Please find the full financial report and presentation enclosed.

EBITDA* and other alternative performance measures (APMs) are defined and reconciled to the IFRS financial statements as a part of the APM section of the second quarter and first half 2023 financial report on page 23.

The quarterly report and presentation will be published at 08:00 CEST and will be publicly available at www.photocure.com. Dan Schneider, CEO and Erik Dahl, CFO, will host a live webcast at 14:00 CEST.

The presentation will be held in English and questions can be submitted throughout the event. The streaming event is available through: https://channel.royalcast.com/hegnarmedia/#!/hegnarmedia/20230809_1

The presentation is scheduled to conclude at 14:45 CEST.

On August 9, 2023 Aadi Bioscience, Inc. (NASDAQ: AADI), a biopharmaceutical company focused on developing and commercializing precision therapies for genetically defined cancers with alterations in mTOR pathway genes, reported a corporate update and announced financial results for the second quarter of 2023 (Press release, Aadi Bioscience, AUG 9, 2023, View Source [SID1234634105]).

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"We are seeing continued growth in FYARRO sales and are pleased with the positive feedback we are receiving from the treatment community," said Scott Giacobello, Interim CEO and President and CFO of Aadi. "The PRECISION1 trial is progressing well, and we are looking forward to providing results of an interim analysis on 40 patients with appropriate follow-up before the end of the year. We expect to complete enrollment as planned in the spring of 2024."

"With PRECISION1 on track, we are excited to announce the expansion of our pipeline to further investigate mTOR pathway inhibition in endometrial cancer and NETs," continued Giacobello. "We are encouraged by the positive feedback received from clinicians, and we believe our preclinical data supporting these programs is promising. We look forward to harnessing the unique pharmacology of nab-sirolimus, both in combination and as monotherapy, to provide enhanced therapeutic benefit in these indications with meaningful patient populations and high unmet need."

Second Quarter 2023 Updates and Recent Operational Highlights

Interim analysis from PRECISION1 expected before the end of 2023. An interim analysis from the tumor agnostic PRECISION1 trial on 40 patients with appropriate follow-up is on track with data expected before the end of 2023. Enrollment continues to be well-balanced between the two arms, and as previously reported, more than 15 discrete tumor types have been enrolled, supporting the thesis that TSC1 and TSC2 alterations occur broadly across different solid tumors.
FYARRO net product sales were $6.2 million in the second quarter, reflecting growth of approximately 6% over Q1 2023 and 80% over the prior year quarter.
Planned initiation of Phase 2 combination trial in endometrial cancer. The Company is initiating a Phase 2 trial investigating the combination of nab-sirolimus with letrozole for the treatment of advanced or recurrent endometrioid-type endometrial cancer (EEC). This is a Phase 2 open-label, multi-institutional study to evaluate the efficacy and safety of nab-sirolimus and letrozole in patients with advanced or recurrent endometrioid endometrial carcinoma. Prior clinical studies with mTOR inhibitors and letrozole in endometrial cancer patients have yielded promising results. In preclinical models, intravenous nab-sirolimus demonstrates significantly higher tumor growth inhibition, intra-tumoral drug accumulation, and greater mTOR target suppression compared with oral inhibitors. The Company is exploring whether the combination of nab-sirolimus with endocrine therapy may produce synergistic anti-tumor activity in patients with EEC. Initiation of this trial is expected in the fourth quarter of 2023.
Planned initiation of Phase 2 study in neuroendocrine tumors (NETs). The Phase 2 study is a multicenter, open-label, single-arm trial that is evaluating adult patients with functional or non-functional, well-differentiated, locally advanced unresectable or metastatic NETs of the GI tract, lung, or pancreas who have received no more than two prior lines of therapy. In preclinical animal models, nab-sirolimus demonstrated improved target suppression relative to similar weekly doses of sirolimus and everolimus, supporting further exploration of nab-sirolimus in NETs. Initiation of this trial is expected in the fourth quarter of 2023.
Initiated Phase 1/2 trial in KRASG12C in collaboration with Mirati Therapeutics. The first patient has been dosed in a Phase 1/2 trial evaluating the combination of adagrasib with nab-sirolimus in this collaborative study. The open-label Phase 1/2 trial is intended to determine the optimal dose and recommended Phase 2 dose in patients with KRASG12C mutant solid tumors.
Multiple posters presented at ASCO (Free ASCO Whitepaper) Annual Meeting 2023. Aadi presented a company-sponsored TIP update from the PRECISION1 Phase 2 study and combination data of nab-sirolimus and pazopanib (PAZO) from an ongoing Investigator Initiated Trial at ASCO (Free ASCO Whitepaper) 2023. The posters are available on the investor relations page of the Aadi website at www.aadibio.com.
Second Quarter 2023 Financial Results

Total revenue resulting from sales of FYARRO for the quarter ended June 30, 2023, was $6.2 million. This compares to the prior year period of $3.4 million.
Cash, cash equivalents and short-term investments as of June 30, 2023, were $134.9 million as compared to $172.6 million as of December 31, 2022, which is expected to fund operations into 2025 based on current plans.
Net loss for the three months ended June 30, 2023, was $18.0 million as compared to $18.3 million for the three months ended June 30, 2022.
Conference Call Information

The Aadi management team is hosting a conference call and webcast today at 8:30 am ET (5:30 am PT) to provide a corporate update and discuss results for the second quarter 2023.

Participants may access a live webcast of the call on the "Investors & News" page of the Aadi Bioscience website at aadibio.com. To participate via telephone, please register in advance at this link. Upon registration, all telephone participants will receive a confirmation email detailing how to join the conference call, including the dial-in number along with a unique passcode and registrant ID that can be used to access the call. A replay of the conference call and webcast will be archived on the Company’s website for at least 30 days.

About FYARRO

FYARRO is an mTOR inhibitor indicated for the treatment of adult patients with locally advanced unresectable or metastatic malignant perivascular epithelioid cell tumor (PEComa).

About the PRECISION1 Trial

The PRECISION1 trial is a multi-center, open-label, tumor-agnostic registrational clinical trial of nab-sirolimus. This tumor agnostic study will evaluate approximately 60 mTOR inhibitor naïve patients in each of two independent study arms, or approximately 120 in total, comprised of patients with solid tumors harboring pathogenic inactivating alterations in either TSC1 or TSC2 genes. In November 2021, the FDA granted Fast Track designation to evaluate nab-sirolimus for this patient population.

nab-Sirolimus 100 mg/m2 is given weekly intravenously over 30 minutes on Days 1 and 8 of each 21-day cycle. The primary endpoint is overall response rate per independent radiographic review (IRR) using RECIST v1.1. Other endpoints include duration of response, time to response, progression-free survival by IRR, overall survival, patient-reported quality of life, and safety.

On August 9, 2023 Merus N.V. (Nasdaq: MRUS) ("Merus", the "Company," "we" and "our"), a clinical-stage oncology company developing innovative, full-length multispecific antibodies (Biclonics and Triclonics), reported the pricing of an underwritten public offering of 6,818,182 common shares, at a public offering price of $22.00 per share (the "Offer Shares") (Press release, Merus, AUG 9, 2023, View Source [SID1234634103]). Merus also granted the underwriters a 30-day option to purchase up to an additional 1,022,727 common shares (the "Option Shares" and together with the Offer Shares, the "Shares"). The gross proceeds from the offering, before deducting underwriting discounts and commissions and estimated offering expenses and excluding the underwriters’ option to purchase the Option Shares, are expected to be approximately $150.0 million. All of the shares in the offering are to be sold by Merus.

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The offering is expected to close on or about August 14, 2023, subject to customary closing conditions.

Merus currently intends to use the net proceeds from the offering, together with its existing cash, cash equivalents and marketable securities, to advance the clinical development of its product candidates, for preclinical research and technology development, and for working capital and general corporate purposes.

Jefferies, BofA Securities, Guggenheim Securities and William Blair are acting as joint book-running managers for the offering. Van Lanschot Kempen is acting as lead manager for the offering.

The offering is being made pursuant to a shelf registration statement on Form S-3 that was filed with the Securities and Exchange Commission (SEC) on May 7, 2021 and was effective upon filing. The offering will be made only by means of a written prospectus and prospectus supplement that form a part of the registration statement, which, for the avoidance of doubt, will not constitute a "prospectus" for the purposes of (i) Regulation (EU) 2017/1129 (the "Prospectus Regulation") and has not been reviewed by any competent authority in any member state in the European Economic Area (the "EEA") and (ii) the Prospectus Regulation as it forms part of domestic law in the United Kingdom by virtue of the European Union (Withdrawal) Act 2018 (the "UK Prospectus Regulation") and has not been reviewed by the Financial Conduct Authority in the United Kingdom. A preliminary prospectus supplement to the prospectus describing the terms of the offering was filed with the SEC on August 9, 2023, and a final prospectus supplement will be filed with the SEC. Copies of the final prospectus supplement and the accompanying prospectus relating to the offering may be obtained, when available, from Jefferies LLC, Attention: Equity Syndicate Prospectus Department, 520 Madison Avenue, New York, NY 10022, by telephone at (877) 821-7388, or by email at [email protected]; BofA Securities NC1-0220-02-25, Attention: Prospectus Department, 201 North Tryon Street, Charlotte, NC 28255‐0001, or by email at [email protected]; Guggenheim Securities, LLC, Attention: Equity Syndicate Department, 330 Madison Avenue, 8th Floor, New York, NY 10017, by telephone at (212) 518-9544, or by email at [email protected]; or William Blair & Company, L.L.C., Attention: Prospectus Department, 150 North Riverside Plaza, Chicago, IL 60606, by telephone at (800) 621-0687, or by email at [email protected].

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

This press release is an advertisement and not a prospectus within the meaning of either the Prospectus Regulation or the UK Prospectus Regulation.

EEA:

In relation to each member state of the EEA (each, a "Relevant State"), no Shares have been offered or will be offered pursuant to the offering to the public in that Relevant State prior to the publication of a prospectus in relation to the Shares which has been approved by the competent authority in that Relevant State or, where appropriate, approved in another Relevant State and notified to the competent authority in that Relevant State, all in accordance with the Prospectus Regulation, except that Shares may be offered to the public in that Relevant State at any time:

to any legal entity which is a "qualified investor" as defined under Article 2 of the Prospectus Regulation;
to fewer than 150 natural or legal persons (other than qualified investors as defined under Article 2 of the Prospectus Regulation), subject to obtaining the prior consent of the representatives for any such offer; and
in any other circumstances falling within Article 1(4) of the Prospectus Regulation,
provided that no such offer of the Shares shall require us or any of the underwriters to publish a prospectus pursuant to Article 3 of the Prospectus Regulation or supplement a prospectus pursuant to Article 23 of the Prospectus Regulation. Each person who initially acquires any Shares or to whom any offer is made will be deemed to have represented, warranted, acknowledged and agreed to and with us and each of the underwriters that it is a "qualified investor" within the meaning of Article 2 of the Prospectus Regulation.

For the purposes of the above, the expression "offer to the public" in relation to the Shares in any Relevant State means the communication in any form and by any means of sufficient information on the terms of the offer and any Shares to be offered so as to enable an investor to decide to purchase or subscribe for any Shares, and the expression "Prospectus Regulation" means Regulation (EU) 2017/1129.

United Kingdom:

No Shares have been offered or will be offered pursuant to this offering to the public in the United Kingdom prior to the publication of a prospectus in relation to the Shares which has been approved by the Financial Conduct Authority in the United Kingdom, except that the Shares may be offered to the public in the United Kingdom at any time:

a) to any legal entity which is a qualified investor as defined under Article 2 of the UK Prospectus Regulation;

b) to fewer than 150 natural or legal persons (other than qualified investors as defined under Article 2 of the UK Prospectus Regulation), subject to obtaining the prior consent of the representatives for any such offer; or

c) in any other circumstances falling within Section 86 of the Financial Services and Markets Act 2000 (the "FSMA")

provided that no such offer of the Shares shall require us or any of the underwriters to publish a prospectus pursuant to Section 85 of the FSMA or Article 3 of the UK Prospectus Regulation or supplement a prospectus pursuant to Article 23 of the UK Prospectus Regulation. Each person in the United Kingdom who initially acquires any Shares or to whom any offer is made will be deemed to have represented, warranted, acknowledged and agreed to and with us and each of the underwriters that it is a "qualified investor" within the meaning of the UK Prospectus Regulation.

For the purposes of this provision, the expression an "offer to the public" in relation to the Shares in the United Kingdom means the communication in any form and by any means of sufficient information on the terms of the offer and any Shares to be offered so as to enable an investor to decide to purchase or subscribe for any Shares.

In addition, in the United Kingdom, the transaction to which this press release relates will only be available to, and will be engaged in only with persons who are "qualified investors" (as defined in the UK Prospectus Regulation) (i) who have professional experience in matters relating to investments falling within Article 19(5) of the FSMA (Financial Promotion) Order 2005, as amended (the Order), and/or (ii) who are high net worth entities (or persons to whom it may otherwise be lawfully communicated) falling within Article 49(2)(a) to (d) of the Order (all such persons together being referred to as "relevant persons"). In the United Kingdom, the securities referred to herein are only available to, and any invitation, offer or agreement to subscribe, purchase or otherwise acquire such securities will be engaged in only with relevant persons. Any person in the United Kingdom who is not a relevant person should not act or rely on this communication or any of its contents.

On August 9, 2023 aTyr Pharma, Inc. (Nasdaq: LIFE) ("aTyr" or the "Company"), a biotherapeutics company engaged in the discovery and development of first-in-class medicines from its proprietary tRNA synthetase platform, reported second quarter 2023 results and provided a corporate update (Press release, aTyr Pharma, AUG 9, 2023, View Source [SID1234634102]).

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"Throughout the second quarter we have continued to progress and invest in our clinical development program for our lead therapeutic candidate, efzofitimod, in interstitial lung disease (ILD)," said Sanjay S. Shukla, M.D., M.S., President and Chief Executive Officer of aTyr. "Our global pivotal Phase 3 EFZO-FIT study in patients with pulmonary sarcoidosis, the most prevalent form of ILD, continues to enroll and our Phase 2 EFZO-CONNECT study in patients with systemic sclerosis (SSc, or scleroderma)-associated ILD (SSc-ILD), is expected to enroll the first patient in the third quarter."

Second Quarter 2023 and Subsequent Period Highlights

Continued enrollment in the global pivotal Phase 3 EFZO-FIT study to evaluate the efficacy and safety of efzofitimod in patients with pulmonary sarcoidosis. This is a randomized, double-blind, placebo-controlled, 52-week study consisting of three parallel cohorts randomized equally to either 3.0 mg/kg or 5.0 mg/kg of efzofitimod or placebo dosed intravenously monthly for a total of 12 doses. The study intends to enroll up to 264 subjects with pulmonary sarcoidosis. The study is open for enrollment at nearly all of the centers intended in the U.S., Europe and Japan and is expected to expand to include centers in Brazil.
Progressed plans to initiate the Phase 2 EFZO-CONNECT study to evaluate the efficacy, safety and tolerability of efzofitimod in patients with SSc-ILD. This proof-of-concept study will be a randomized, double-blind, placebo-controlled, 28-week study consisting of three parallel cohorts randomized 2:2:1 to either 270 mg or 450 mg of efzofitimod or placebo dosed intravenously monthly for a total of 6 doses. The study is expected to enroll 25 patients at multiple centers in the U.S. The primary objective of the study will be to evaluate the efficacy of multiple doses of intravenous efzofitimod on pulmonary, cutaneous and systemic manifestations in patients with SSc-ILD. The study is expected to initiate in the third quarter of 2023.
Received European Commission orphan drug designation for efzofitimod for the treatment of SSc based on the opinion of the European Medicines Agency (EMA) Committee for Orphan Medicinal Products. The EMA grants orphan status to products intended for the treatment, prevention or diagnosis of a disease with a prevalence no more than five in 10,000 people in the EU that is life-threatening or chronically debilitating for which either no satisfactory method of diagnosis, prevention, or treatment exists, or if such a method exists, the medicine is of significant benefit to those affected by such condition. EMA orphan drug designation provides certain benefits, including the potential for up to 10 years of marketing exclusivity following regulatory approval in the EU, reduction in regulatory fees and a centralized EU approval process.
Announced two posters for efzofitimod accepted for presentation at the upcoming European Respiratory Society (ERS) International Congress 2023. The conference is scheduled to take place September 9 – 13, 2023, in Milan, Italy. The Company will present new data from a pooled, post hoc analysis from the Phase 1b/2a study of efzofitimod in patients with pulmonary sarcoidosis that further supports efficacy measures in these patients. Additionally, new mechanistic data supports the rationale for efzofitimod as a potential treatment for patients with SSc-ILD.
Poster PA419 – Efzofitimod: A Novel Therapeutic Candidate for SSc-ILD on Sunday, September 10, 2023, from 8:00 a.m. to 9:30 a.m. CEST.
Poster PA1744 – Therapeutic Doses of Efzofitimod Significantly Improve Multiple Pulmonary Sarcoidosis Efficacy Measures on Sunday, September 10, 2023, from 4:00 p.m. to 5:30 p.m. CEST.
Second Quarter 2023 Financial Highlights and Cash Position

Cash & Investment Position: Cash, restricted cash, cash equivalents and investments as of June 30, 2023, were $112.0 million. Based on the Company’s current operational plans and existing cash, the Company maintains its prior guidance and believes its cash runway will extend into 2026.
R&D Expenses: Research and development expenses were $9.8 million for the second quarter of 2023, which consisted primarily of clinical trial costs for the Phase 3 EFZO-FIT study, manufacturing costs for the efzofitimod program and research and development costs for the efzofitimod and discovery programs.
G&A Expenses: General and administrative expenses were $3.7 million for the second quarter of 2023.
About Efzofitimod

aTyr is developing efzofitimod as a potential therapeutic for patients with fibrotic lung disease. Efzofitimod, a fusion protein comprised of the immunomodulatory domain of histidyl-tRNA synthetase fused to the FC region of a human antibody, is a selective modulator of neuropilin-2 that downregulates innate immune responses in inflammatory disease states. aTyr’s lead indication for efzofitimod is pulmonary sarcoidosis, a major form of interstitial lung disease. Clinical proof-of-concept for efzofitimod was recently established in a Phase 1b/2a multiple-ascending dose, placebo-controlled study of efzofitimod in patients with pulmonary sarcoidosis, which demonstrated safety and a consistent dose response and trends of benefit of efzofitimod compared to placebo on key efficacy endpoints, including steroid reduction, lung function, clinical symptoms and inflammatory biomarkers. aTyr is currently conducting EFZO-FIT, a Phase 3 study of efzofitimod in pulmonary sarcoidosis patients.

On August 9, 2023 Mirati Therapeutics, Inc. (NASDAQ: MRTX), a commercial stage biotechnology company, reported Cancer Discovery published preclinical and initial clinical data from a first-in-human Phase 1/2 clinical trial of MRTX1719, a PRMT5 / methylthioadenosine (MTA)-cooperative inhibitor evaluated in methylthioadenosine phosphorylase (MTAP) deleted cancers (Press release, Mirati, AUG 9, 2023, View Source [SID1234634100]). These results provide preclinical and early clinical proof-of-concept for this differentiated approach and demonstrate that MRTX1719 may represent a promising targeted therapy for the ~10% of cancer patients with this biomarker. The publication can be found here.

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In preclinical studies, MRTX1719 was demonstrated to be a potent, selective inhibitor of the PRMT5/MTA complex. This compound exploits the elevated MTA levels present in MTAP-deleted cancers and turns this altered metabolic state into a therapeutic vulnerability to selectively kill MTAP deleted cancer cells while sparing normal cells. Preclinical results showed marked anti-tumor activity of MRTX1719, including regression, across lung, pancreatic, mesothelioma, and other solid tumor models.

As of June 13, 2023, there were 18 patients with solid tumors harboring MTAP deletions in the Phase 1/2 trial of MRTX1719 that were evaluable for clinical response at dose levels of 100mg QD or greater. Initial dose level started at 50mg administered once-daily orally over 21-day cycles followed by 100% dose escalations for subsequent dose levels. Six individual case narratives were selected for inclusion in the Cancer Discovery publication:

There were six confirmed objective responses observed in the Phase 1 study including one patient who achieved a response which subsequently confirmed post-data cutoff
MRTX1719 achieved apparent complete PRMT5 inhibition in MTAP deleted tumor cells at a dose of 200 mg QD as evidenced by pretreatment and on-treatment tumor biopsies of the PRMT5 biochemical biomarker symmetric dimethyl arginine (SDMA)
It was notable that four patients were on therapy for multiple cycles before experiencing an initial objective response, with their tumors continuing to decrease in size over the course of treatment.
These findings suggest that tumor response may continue to deepen over time indicating the importance of evaluating tumor response kinetics and response rates across a broader patient population with longer follow up.
MRTX1719 was well-tolerated with no dose limiting toxicities observed at dose levels up to 400mg QD. None of the patients treated with MRTX1719 experienced dose-limiting adverse events associated with first generation PRMT5 inhibitors such as thrombocytopenia, anemia or neutropenia.
"Many cancers with a prevalence of MTAP deletion have few treatment options so it is encouraging to see these initial responses in the clinic. These data, including the favorable safety profile, demonstrate the development of a possible therapeutic approach for a significant population of patients with MTAP-deleted cancers in need of new treatment options," said Jordi Rodon Ahnert, MD, PhD, The University of Texas MD Anderson Cancer Center. "It will be important for next-generation sequencing tests to expand their panel of targets to include for markers of PRMT5 inhibition."

"The targeting strategy of MRTX1719 is differentiated from first generation PRMT5 inhibitors and has so far shown to be well tolerated in this patient population with dire unmet need," said James Christensen, Ph.D., chief scientific officer, Mirati Therapeutics, Inc. "We are pleased that Cancer Discovery recognized the importance and potential impact of this early data from MRTX1719, and we look forward to pursuing continued development of MRTX1719 for the benefit of patients living with cancer."

About MRTX1719 (MTA-cooperative PRMT5 inhibitor)

MRTX1719, discovered at Mirati, is an orally bioavailable, methylthioadenosine (MTA)-cooperative PRMT5 inhibitor that exhibits synthetic lethality in MTAP-deleted cancers. MTAP deletion leads to MTA accumulation in cancer cells and MRTX1719 is designed to selectively bind the PRMT5-MTA complex ultimately inhibiting PRMT5 function in MTAP-deleted cancer cells while sparing healthy non-tumor cells.1MTAP deletions occur in around 10% of all cancers2, including a high percentage of pancreatic cancer, non-small cell lung cancer, and mesothelioma which are associated with a poor prognosis, representing a significant unmet medical need. The PRMT5-MTA complex creates a novel drug target for the treatment of MTAP-deleted cancers. Targeting this complex involves a new and potentially improved therapeutic approach. MRTX1719 is being evaluated as monotherapy and in combination with other therapeutic options to treat patients with advanced, unresectable or metastatic solid tumor malignancy with homozygous deletion of the MTAP gene.

For more information visit Mirati.com/science.