On August 9, 2023 Repare Therapeutics Inc. ("Repare" or the "Company") (Nasdaq: RPTX), a leading clinical-stage precision oncology company, reported financial results for the second quarter ended June 30, 2023 (Press release, Repare Therapeutics, AUG 9, 2023, View Source [SID1234634090]).

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"During the second quarter we made great progress advancing our clinical programs and presenting novel findings from our ongoing clinical trials, including reporting on camonsertib’s combination with three PARP inhibitors and initial clinical proof of concept for lunresertib," said Lloyd M. Segal, President and Chief Executive Officer of Repare. "While these clinical programs move towards Phase 2 studies, we continue to support our preclinical pipeline, for example with the designation of our Polθ inhibitor, RP-3467. We look forward to reporting initial combination data of lunresertib with camonsertib in the fourth quarter of this year as we continue advancing our differentiated, synthetic lethal-based oncology pipeline."

Second Quarter 2023 Review and Operational Updates:

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Advancing camonsertib, a potent and selective oral small molecule inhibitor of ATR (Ataxia-Telangiectasia and Rad3-related protein kinase) for the treatment of tumors with specific synthetic lethal genomic alterations in partnership with Roche.
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Roche has included a camonsertib-based arm in its Phase 2, global, multicenter, open-label, multi-cohort TAPISTRY study (NCT04589845) and its Phase 1/2 study of multiple immunotherapy-based treatment combinations in participants with metastatic non-small cell lung cancer (Morpheus Lung; NCT03337698). Repare is eligible to receive a milestone payment of $40 million upon dosing of the first patient with camonsertib in the TAPISTRY study and could be eligible for an additional $15 million milestone if this study becomes registrational.

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Repare is continuing to conduct dose optimization and efficacy assessments in tumor specific expansions in the ATTACC study in collaboration with Roche to support future clinical development plans for camonsertib combinations with PARP inhibitors. In April 2023, we received a payment of $4 million from Roche for additional revisions to the clinical development plan under the Roche Agreement. Repare is eligible to receive further milestone payments upon the initiation of registrational trials or the transition of existing trials to become registrational for camonsertib in specific tumor types.
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Published data in Nature Medicine from the ongoing Phase 1/2 TRESR clinical trial evaluating camonsertib monotherapy in 120 patients (NCT04497116). The article, entitled "Camonsertib in DNA damage response-deficient advanced solid tumors: phase 1 trial results" can be accessed at View Source
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Announced initial clinical data from the Phase 1/2 TRESR and ATTACC trials evaluating camonsertib in combination with three poly (ADP-ribose) polymerase (PARP) inhibitors in a Clinical Trials Plenary Session at the 2023 American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting.
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Camonsertib-PARP inhibitor combinations appeared to be well tolerated and resulted in durable clinical benefit across tumor types and genomic alterations, regardless of choice of PARP inhibitor and presence of platinum resistance. Overall clinical benefit rate (CBR) for all patients was 48%. Patients with platinum-resistant tumors had an overall response rate (ORR) of 12% and CBR of 49% and benefited similarly to non-platinum-resistant tumors (ORR 13%, CBR 46%). Compelling results were observed particularly in patients with advanced ovarian cancer (n=19), including overall response of 32%, CBR of 58% and median progression-free survival of approximately 7 months with treatment greater than 16 weeks and ongoing in 9 patients, as of the 2023 AACR (Free AACR Whitepaper) Annual Meeting data cutoff of February 27, 2023. The molecular response rate (MRR) of circulating tumor DNA was significantly higher in patients with clinical benefit (83%) compared to those without (48%; p=0.015) and significantly higher than seen in the camonsertib monotherapy trial in which camonsertib was administered at higher doses (66% vs. 43%; p=0.02). Molecular responses were also observed in patients with prior PARP inhibitor exposure (57%) and platinum resistance (64%).
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Advancing lunresertib (RP-6306), a first-in-class, oral PKMYT1 inhibitor, for the treatment of molecularly select advanced solid tumors as a monotherapy and in combinations in multiple clinical studies.
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Announced clinical proof of concept for lunresertib, including monotherapy data from the Phase 1 MYTHIC clinical trial and early insights from ongoing combination trials in June 2023. Achieved primary endpoints of safety and tolerability and proposed dose and schedule. The tolerability profile of lunresertib monotherapy appears favorable and differentiated from other clinical cell cycle inhibitors, as lunresertib treatment does not result in significant myelotoxicity nor diarrhea. No grade 4 toxicity was observed with lunresertib, while grade 3 treatment emergent adverse events of interest included rash (7.9%), anemia (6.3%) and nausea or vomiting (1.6%). The dose limiting toxicity was reversible rash, alleviated with dose modifications and simple supportive measures. Two proposed dose/schedules were identified – 240mg daily continuously and 80-100mg BID intermittent weekly – to offer maximum flexibility in combination studies.
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Preliminary anti-tumor activity was observed for monotherapy, including moderate tumor shrinkages and a confirmed partial response per RECIST 1.1 criteria in a patient with metastatic recurrent uterine carcinosarcoma.

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Early clinical responses per RECIST 1.1 criteria have been observed with lunresertib and combinations with gemcitabine, camonsertib, and FOLFIRI in multiple tumor types and genotypes.
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Repare is collaborating with Princess Margaret Cancer Center to initiate clinical testing, as part of an investigator-sponsored trial (IST) of a fourth lunresertib combination with carboplatin and paclitaxel for the treatment of recurrent gynecological malignancies, with first patient dosing expected this year.
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Repare is also collaborating with the Canadian Cancer Trials Group in an ongoing basket Phase 2 IST that is enrolling patients with selected, advanced cancers receiving lunresertib as combination with gemcitabine (NCT05605509), and in a second active study that will evaluate lunresertib in combination with gemcitabine in patients with CDK4/6 inhibitor treated ER+/HER2- metastatic breast cancer (NCT05601440).
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In August 2023, the U.S. Food and Drug Administration (FDA) granted Fast Track designation (FTD) to lunresertib in combination with camonsertib for the treatment of adult patients with CCNE1 amplified, or FBXW7 or PPP2R1A mutated endometrial cancer previously treated with a platinum-containing regimen and immune checkpoint inhibitor when indicated. FTD is intended to facilitate the development and expedite the review of drugs to treat serious conditions and fulfill an unmet medical need, enabling drugs to reach patients earlier.
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The Company expects to present further Phase 1 MYTHIC Module 2 combination data with camonsertib at a medical conference in the fourth quarter of this year.
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Advancing preclinical programs into clinical development.
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RP-1664 IND-enabling studies, which began in the first quarter of 2023, remain ongoing with potential for the program to enter the clinic in early 2024.
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Initiated IND-enabling studies for the newly designated Polθ inhibitor RP-3467 in June 2023. RP-3467 has shown greater potency in preclinical studies compared to RP-2119, our first Polθ inhibitor designated in 2022, and has potential to enter the clinic in 2024. The research term of our Polθ collaboration with Ono Pharmaceutical Company Ltd., as previously extended, expired on July 31, 2023. With the termination of the agreement with Ono Pharmaceutical Company Ltd., Repare’s Polθ program, including RP-3467, is wholly-owned by Repare.
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The Company intends to host an R&D day focused on its ongoing pre-clinical programs and its overall pipeline in the fourth quarter of this year.
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In May 2023, Bristol Myers Squibb exercised its option for a third druggable target and separately triggered a $1 million payment for a previously exercised druggable target option.
Second Quarter 2023 Financial Results:

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Cash and cash equivalents and marketable securities: Cash and cash equivalents and marketable securities as of June 30, 2023 were $280.7 million, which Repare believes will be sufficient to fund its planned operations into 2026.
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Revenue from collaboration agreements: Revenue from collaboration agreements were $30.2 million and $35.9 million for the three and six months ended June 30, 2023, respectively, as compared to $0.7 million and $1.1 million for the three and six months ended June 30, 2022. The increase in revenue for the three- and six-month periods were primarily due to revenue recognized from our collaboration and license agreement with BMS and our collaboration agreement with Ono.

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Research and development expenses, net of tax credits (Net R&D): Net R&D expenses were $33.8 million and $65.6 million for the three and six months ended June 30, 2023, respectively, as compared to $31.5 million and $57.9 million for the three and six months ended June 30, 2022. The increase in Net R&D expenses for the three- and six-month periods was primarily due to higher personnel-related costs and direct external costs related to the advancement of preclinical programs into IND-enabling studies.
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General and administrative (G&A) expenses: G&A expenses were $8.7 million and $17.2 million for the three and six months ended June 30, 2023, respectively, compared to $7.9 million and $16.7 million for the three and six months ended June 30, 2022. The increase in G&A was primarily due higher personnel related costs, offset by lower D&O insurance premiums.
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Net loss: Net loss was $11.9 million, or $0.28 per share, and $46.9 million, or $1.11 per share, in the three and six months ended June 30, 2023, respectively, and $38.1 million, or $0.91 per share, and $72.9 million, or $1.74 per share, in the three and six months ended June 30, 2022, respectively.

On August 9, 2023 Precigen, Inc. (Nasdaq: PGEN), a biopharmaceutical company specializing in the development of innovative gene and cell therapies to improve the lives of patients, reported second quarter and first half 2023 financial results and business updates (Press release, Precigen, AUG 9, 2023, View Source [SID1234634089]).

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"Today we announced that the FDA confirmed the ongoing Phase 1/2 study of PRGN-2012 will serve as the pivotal study to support accelerated approval, an important milestone that brings Precigen a step closer in our transition to a commercial stage company and in realizing our vision of bringing life-changing therapies to patients with unmet medical need. We look forward to working with the FDA to submit a BLA and potentially bringing the first drug therapy for RRP patients. As a result of this exciting milestone, we are prioritizing our portfolio activities to maximize the potential success of PRGN-2012 while continuing to strategically advance other key programs," said Helen Sabzevari, PhD, President and CEO of Precigen. "We have built a strong portfolio based on the AdenoVerse and UltraCAR-T platforms and continue to advance important programs with a focus on agility, efficiency and commercial viability."

"As a result of our capital raise in January, our portfolio prioritization and other cost-saving measures, including completely retiring our convertible notes, the Company’s balance sheet is well positioned for the future," said Harry Thomasian Jr., CFO of Precigen. "These measures have enabled us to extend our projected cash runway into 2025, exclusive of non-dilutive strategies, including strategic partnerships, which could extend our cash runway further."

Program Highlights

PRGN-2012 AdenoVerse Immunotherapy in RRP

· The Company announced that the the US Food and Drug Administration (FDA) has agreed that the ongoing Phase 1/2 single arm study of the first-in-class investigational PRGN-2012 AdenoVerse immunotherapy for the treatment of recurrent respiratory papillomatosis (RRP) will serve as pivotal for the purpose of filing an accelerated approval request for licensure. The FDA also confirmed no additional randomized, placebo-controlled trial will be required to support submission of a biologics license application (BLA). Based on the FDA guidance, the Company also plans to initiate a confirmatory study prior to submission of the BLA.
· PRGN-2012 is an investigational off-the-shelf AdenoVerse immunotherapy designed to elicit immune responses directed against cells infected with human papillomavirus (HPV) 6 or HPV 11 for the treatment of RRP.
· The Company completed enrollment and dosing in the Phase 2 portion of the study (N=23) bringing the total number of enrolled patients to 35 at the recommended Phase 2 dose. Patient follow up is currently ongoing and data collection is anticipated to be completed by the second quarter of 2024.
· The Company announced that the FDA granted Breakthrough Therapy Designation for PRGN-2012 for the treatment of RRP, adding to the existing Orphan Drug Designation. The Breakthrough designation is based on
positive Phase 1 clinical data that showed that 50% of adult RRP patients (who had ≥3 surgeries to treat the disease in the year prior treatment) were "surgery-free" (Complete Response) after PRGN-2012 treatment during the 12 month follow-up. All complete responders continue to be surgery-free with a minimum follow-up of 18 months post-treatment.

PRGN 2009 AdenoVerse Immunotherapy in HPV-associated Cancers

· PRGN-2009 is an investigational off-the-shelf AdenoVerse immunotherapy designed to activate the immune system to recognize and target HPV-positive solid tumors.
· The Company completed the Phase 1 study and presented positive Phase 1 clinical data from the monotherapy (N=6) and combination therapy (N=11) arms in patients with recurrent or metastatic HPV-associated cancers at the 2023 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting. PRGN-2009 was safe and well-tolerated with only Grade 1 or 2 treatment related adverse events and resulted in a 30% objective response rate (ORR) in the combination arm in patients with heavily pre-treated HPV-associated cancers that were naïve or resistant to checkpoint blockade with prolonged duration of responses.
· Enrollment was completed in the Phase 2 monotherapy arm with 20 evaluable patients in newly diagnosed oropharyngeal squamous cell carcinoma (OPSCC) patients.
· The Company announced that the FDA has cleared the Investigational New Drug (IND) application to initiate a Phase 2 study of PRGN-2009 in combination with pembrolizumab in patients with recurrent or metastatic cervical cancer. The Phase 2 randomized, open-label, two-arm study will evaluate the efficacy and safety of PRGN-2009 in combination with pembrolizumab versus pembrolizumab monotherapy in patients with recurrent or metastatic cervical cancer who are pembrolizumab resistant.

PRGN-3006 UltraCAR-T in AML

· PRGN-3006 is an investigational multigenic, autologous chimeric antigen receptor T (CAR-T) cell therapy engineered to express a CAR specifically targeting CD33, membrane bound IL-15 (mbIL15), and a kill switch. The FDA granted Orphan Drug Designation and Fast Track Designation for PRGN-3006 UltraCAR-T for patients with relapsed or refractory acute myeloid leukemia (AML).
· The Company completed the Phase 1 dose escalation study and announced positive data at the 64th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting and Exposition. PRGN-3006 was well-tolerated with no dose-limiting toxicities. A single infusion of autologous PRGN-3006 cells resulted in a 27% ORR in heavily pre-treated relapsed or refractory AML patients infused following lymphodepletion. A single infusion of UltraCAR-T cells with or without lymphodepletion demonstrated robust expansion and persistence in blood and bone marrow and PRGN-3006 infusion with lymphodepletion resulted in a decrease in bone marrow blasts in 60% of heavily pre-treated patients.
· The Phase 1b dose expansion study of PRGN-3006 is ongoing and an interim clinical data presentation is expected in 2024.

PRGN-3005 UltraCAR-T in Ovarian Cancer

· PRGN-3005 UltraCAR-T is an investigational multigenic, autologous CAR-T cell therapy engineered to express a CAR specifically targeting the unshed portion of MUC16, mbIL15, and a kill switch.
· The Company completed the Phase 1 dose escalation cohorts of the intraperitoneal (IP) and intravenous (IV) arms without lymphodepletion as well as in the lymphodepletion cohort in the IV arm and presented positive Phase 1 clinical data in patients with advanced platinum resistant ovarian cancer at the 2023 ASCO (Free ASCO Whitepaper) Annual Meeting. PRGN-3005 was well-tolerated with no dose-limiting toxicities, no cytokine release syndrome (CRS) greater than Grade 2, and no neurotoxicity. PRGN-3005 cells demonstrated expansion and persistence when delivered via either IP or IV infusion without lymphodepletion or via IV infusion after lymphodepletion. A single IV infusion following lymphodepletion decreased tumor burden in 67% of the heavily pretreated patients (median of 8 or more prior therapies).
· The Phase 1b dose expansion study of PRGN-3005 is ongoing.

PRGN-3007 UltraCAR-T in Advanced ROR1+ Hematological and Solid Tumors

· PRGN-3007, based on the next generation of the UltraCAR-T platform, is an investigational multigenic, autologous CAR-T cell therapy engineered to express a CAR targeting receptor tyrosine kinase-like orphan receptor 1 (ROR1), mbIL15, a kill switch, and a novel mechanism for the intrinsic blockade of PD-1 gene expression.
· The Phase 1 dose escalation part of the Phase 1/1b study is ongoing. The target patient population for the Phase 1/1b study includes hematological cancers (chronic lymphocytic leukemia (CLL), mantle cell lymphoma (MCL), acute lymphoblastic leukemia (ALL), and diffuse large B-cell lymphoma (DLBCL)) and solid tumors (triple negative breast cancer (TNBC)).

Financial Highlights

· Completely retired the outstanding balance of convertible notes in the second quarter.
· Cash, cash equivalents, short-term and long-term investments totaled $95.6 million as of June 30, 2023.
· Selling, general, and administrative (SG&A) costs decreased versus the prior year, by 27% and 21% for the three and six months ended June 30, 2023, respectively.

Second Quarter 2023 Financial Results Compared to Prior Year Period

Research and development expenses decreased $0.1 million, or 0.7%, compared to the three months ended June 30, 2022. This decrease was primarily driven by reduced spending on preclinical research programs.

SG&A expenses decreased $3.4 million, or 27%, compared to the three months ended June 30, 2022. This decrease was primarily driven by a reduction in professional fees of $2.2 million, due to decreased legal fees associated with certain litigation matters, as well as a $1.1 million reduction in salaries, benefits, and other personnel costs due to reduced head count.

Revenues decreased $1.1 million, or 39%, compared to the three months ended June 30, 2022. This decrease was related to reductions in services performed at Exemplar.

Total other income, net, increased $2.7 million compared to the three months ended June 30, 2023. This was primarily due to reduced interest expense associated with the Company’s convertible notes as they were retired in the second quarter of 2023, and increased interest income due to higher interest rates on investments.

Loss from continuing operations was $20.3 million, or $(0.08) per basic and diluted share, compared to loss from continuing operations of $26.1 million, or $(0.13) per basic and diluted share, in Q2 2022.

First Half 2023 Financial Results Compared to Prior Year Period

Research and development expenses increased $0.3 million, or 1.2%, compared to the six months ended June 30, 2022. This increase was primarily driven by a continued prioritization of clinical product candidates, offset by reduced spending on preclinical research programs.

SG&A expenses decreased $5.4 million, or 21%, compared to the six months ended June 30, 2022. This decrease was primarily driven by a reduction in professional fees of $4.2 million, due to decreased legal fees associated with certain litigation matters, as well as a $1.1 million reduction in salaries, benefits, and other personnel costs due to reduced head count.

Revenues decreased $4.8 million, or 57.1%, compared to the six months ended June 30, 2022. This decrease was primarily related to reductions in services performed at Exemplar as well as the recognition of revenue in the first quarter of 2022 related to agreements for which revenue was previously deferred that did not occur in 2023 of $1.0 million at Exemplar.

Total other income, net, increased $5.2 million compared to the six months ended June 30, 2022. This was primarily due to reduced interest expense associated with the Company’s convertible notes as they were retired in the second quarter of 2023, and increased interest income due to higher interest rates on investments.

Loss from continuing operations was $43.1 million, or $(0.18) per basic and diluted share, compared to loss from continuing operations of $50.0 million, or $(0.25) per basic and diluted share, in the six months ended June 30, 2022. The 2023 second quarter loss was lower than the 2023 first quarter loss primarily due to continued reductions in SG&A expenses.

On August 9, 2023 PMV Pharmaceuticals, Inc. (Nasdaq: PMVP), a precision oncology company pioneering the discovery and development of small molecule, tumor agnostic therapies targeting p53, reported financial results for the second quarter ended June 30, 2023, and provided a corporate update (Press release, PMV Pharma, AUG 9, 2023, View Source [SID1234634088]).

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PMV recently concluded an End-of-Phase 1 meeting with the U.S. Food and Drug Administration (FDA) focused on gaining alignment with the Agency regarding the clinical and regulatory pathway for developing PC14586 for the treatment of patients with locally advanced or metastatic solid tumors that have a p53 Y220C mutation. Alignment with the FDA was obtained on the recommended Phase 2 dose as well as key elements of the Phase 2 registrational portion of the PYNNACLE trial. PMV plans to initiate the single arm, Phase 2 portion of the PYNNACLE study in early 2024.

"Our ongoing PYNNACLE study of PC14586 in patients with advanced solid tumors continues to make good progress," said David Mack, Ph.D., President and Chief Executive Officer. "The positive outcome of our recently held End-of-Phase 1 meeting positions us to initiate a registrational trial for PC14586 and is an important milestone in our goal of bringing PC14586 to advanced cancer patients with a p53 Y220C mutation. Furthermore, we look forward to sharing updated Phase 1 data in the second half of the year."

Dr. Mack added, "We are also very pleased to welcome Dr. Masha Poyurovsky to PMV as Vice President of Biology. Her scientific expertise in p53 biology and proven track record in translational drug development make her the ideal candidate to lead our biology team. I look forward to Masha’s leadership and contributions as we continue to leverage the potential of p53 targeted therapies."

Second Quarter 2023 and Recent Corporate Highlights:

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Ongoing enrollment in the combination arm of PYNNACLE evaluating PC14586 with KEYTRUDA (pembrolizumab). PMV and Merck entered into a collaboration in 2022 under the terms of which Merck will supply KEYTRUDA for this study.

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Appointed Masha Poyurovsky, Ph.D., as Vice President of Biology. Dr. Poyurovsky has more than a decade of experience leading novel platforms and a track record of advancing therapies from concept to the clinic. From 2011 to 2023, she was employed at Kadmon (acquired by Sanofi in 2021) most recently as Vice President, Discovery Biology. Prior to working in industry, she was a Research Scientist and a Postdoctoral Research Fellow at Columbia University where she conducted studies on p53 in the laboratory of Professor Carol Prives. She is the author and co-author of numerous publications and patents in the area of cancer biology and drug discovery. Dr. Poyurovsky obtained a

doctorate in biochemistry from Columbia University and a bachelor of science in biochemistry and biophysics from the University of Pittsburgh.

Second Quarter 2023 Financial Results

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PMV Pharma ended the second quarter with $218.8 million in cash, cash equivalents, and marketable securities, compared to $277.4 million as of June 30, 2022. Net cash used in operations was $27.9 million for the six months ended June 30, 2023, compared to $31.7 million for the six months ended June 30, 2022.
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Net loss for the six months ended June 30, 2023, was $36.6 million compared to $35.7 million for the six months ended June 30, 2022.
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Research and development (R&D) expenses were $28.9 million for the six months ended June 30, 2023, compared to $23.3 million for the six months ended June 30, 2022. The increase in R&D expenses was primarily related to increased headcount and clinical expenses to advance research on PC14586, the Company’s lead drug candidate.
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General and administrative (G&A) expenses were $12.7 million for the six months ended June 30, 2023, compared to $13.2 million for the six months ended June 30, 2022. The decrease in G&A expenses was primarily due to facility related costs now allocated to research as our new laboratory building in Princeton, New Jersey began operations.

KEYTRUDA (pembrolizumab) is a registered trademark of Merck Sharp & Dohme LLC., a subsidiary of Merck & Co., Inc., Rahway, NJ, USA.

About PC14586

PC14586 is a first-in-class, small molecule, p53 reactivator designed to selectively bind to the crevice present in the p53 Y220C mutant protein, hence, restoring the wild-type, or normal, p53 protein structure and tumor-suppressing function. The U.S. Food and Drug Administration granted Fast Track designation to PC14586 for the treatment of patients with locally advanced or metastatic solid tumors that have a p53 Y220C mutation. For more information about the Phase 1/2 PYNNACLE trial (PMV-586-101), refer to www.clinicaltrials.gov (NCT study identifier NCT04585750).

On August 9, 2023 Pliant Therapeutics, Inc. (Nasdaq: PLRX), a clinical stage biotechnology company focused on discovering and developing novel therapeutics for the treatment of fibrosis, reported a corporate update and provided second quarter 2023 financial results (Press release, Pliant Therapeutics, AUG 9, 2023, View Source [SID1234634087]).

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"We are extremely pleased with the continued progress in the second quarter across the portfolio, including positive long-term data from our INTEGRIS-IPF Phase 2a trial of bexotegrast in IPF, as well as the entry of our third drug candidate, PLN-101095, into Phase 1 testing for treatment of solid tumors. Our team’s strong execution over the quarter positions us well for multiple expected milestones throughout the remainder of the year, including the recent initiation of BEACON-IPF, our Phase 2b trial in IPF, and an upcoming interim Phase 2a data readout from INTEGRIS-PSC which is expected in the third quarter," said Bernard Coulie, M.D., Ph.D., President and Chief Executive Officer of Pliant Therapeutics.

Second Quarter and Recent Highlights

Bexotegrast Highlights

•BEACON-IPF, a Phase 2b trial of bexotegrast in patients with IPF, has been initiated. BEACON-IPF is a 52-week, multinational, randomized, dose-ranging, double-blind, placebo-controlled trial evaluating bexotegrast at once-daily doses of 160 mg or 320 mg. BEACON-IPF is expected to enroll approximately 270 patients with IPF.
•INTEGRIS-IPF Phase 2a 24-week 320 mg clinical data showed bexotegrast was well tolerated and demonstrated durable improvements in exploratory efficacy endpoints. Phase 2a 24-week data from the 320 mg dose cohort showed bexotegrast was well tolerated up to 40 weeks, displayed a favorable pharmacokinetic profile and showed durable improvements in forced vital capacity (FVC), Quantitative Lung Fibrosis (QLF) imaging, patient reported cough severity and fibrosis biomarkers in patients with idiopathic pulmonary fibrosis (IPF).
•INTEGRIS-PSC Phase 2a 12-week interim data expected in the third quarter of 2023. INTEGRIS-PSC is a randomized, dose-ranging, double-blind, placebo-controlled trial evaluating the safety, tolerability and pharmacokinetics of bexotegrast in patients with primary sclerosing cholangitis (PSC). Exploratory efficacy endpoints include fibrosis biomarkers such as PRO-C3 and enhanced liver fibrosis (ELF) score, changes in alkaline phosphatase (ALP), and liver imaging. Interim 12-week data from approximately 84 patients in the 40, 80 and 160 mg cohorts is expected in the third quarter of 2023.
•INTEGRIS-PSC 320 mg dose cohort enrollment complete with interim 12-week data expected in the first quarter of 2024. This trial is evaluating the safety, tolerability and pharmacokinetics of bexotegrast at 320 mg versus placebo at 12 and 24 weeks of treatment in approximately 28 patients with PSC. The trial is also evaluating exploratory efficacy endpoints including fibrosis biomarkers such as serum PRO-C3 and ELF score, changes in ALP and liver imaging. The final 24-week data is expected in mid-2024.
Pipeline Programs
•Phase 1 trial of PLN-101095 in solid tumors recruiting. A Phase 1 open label trial of PLN-101095, an oral, small-molecule, dual selective inhibitor of αvβ8 and αvβ1 integrins designed to block TGF-β activation in the tumor microenvironment, was initiated in the second quarter. This trial is recruiting patients with solid tumors that are resistant to immune checkpoint inhibitors.
•Muscular dystrophy program progressing through IND enabling activities. PLN-101325 is a monoclonal antibody designed to act as an allosteric agonist of the α7β1 integrin. An IND submission for PLN-101325 for Duchenne muscular dystrophy (DMD) is expected in the first quarter of 2024.
Corporate Highlights
•Scott Turner, Ph.D. promoted to Chief Scientific Officer. The Company is announcing the promotion of Dr. Scott Turner to the role of Chief Scientific Officer. Dr. Turner joined Pliant in 2016 and most recently served as the Company’s Senior Vice President of Research. In his new role, Dr. Turner will oversee all early stage drug discovery initiatives and manage the Company’s development portfolio.
Second Quarter 2023 Financial Results
•Research and development expenses were $33.0 million, as compared to $26.3 million for the prior-year quarter. The increase was due primarily to employee related expenses and increased clinical and manufacturing-related costs associated with our lead program, bexotegrast, partially offset by a decrease in preclinical manufacturing costs for our pipeline product candidates.
•General and administrative expenses were $14.6 million, as compared to $8.3 million for the prior-year quarter. The increase was due to higher personnel-related expenses.
•Net loss of $41.2 million as compared to $29.5 million for the prior-year quarter due to an increase in operating expenses coupled with a decrease in collaboration revenues under the Novartis collaboration during the quarter.
•As of June 30, 2023, the Company had cash, cash equivalents and short-term investments of $555.2 million which the Company expects to be sufficient to fund operations into the second half of 2026.

On August 9, 2023 Omeros Corporation (Nasdaq: OMER), a clinical-stage biopharmaceutical company committed to discovering, developing and commercializing small-molecule and protein therapeutics for large-market and orphan indications targeting immunologic disorders including complement-mediated diseases, cancers, and addictive and compulsive disorders, reported recent highlights and developments as well as financial results for the second quarter ended June 30, 2023, which include (Press release, Omeros, AUG 9, 2023, View Source [SID1234634085]):

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● Net loss was $37.3 million in the quarter ended June 30, 2023, or $0.59 per share, compared to a net loss in the prior year quarter of $30.8 million, or $0.49 per share. For the six months ended June 30, 2023 our net loss was $71.0 million, or $1.13 per share compared to $63.9 million, or $1.02 per share in the prior year period. Cash burn for the second quarter was $30.1 million.

● For the second quarter of 2023, we earned OMIDRIA royalties of $10.7 million on Rayner Surgical Inc.’s ("Rayner") U.S. net sales of $35.7 million. This compares to earned royalties of $17.2 million during the second quarter of the prior year on U.S. net sales of $34.5 million. The base royalty rate applicable to U.S. net sales of OMIDRIA decreased from 50 percent to 30 percent in December 2022 upon recognition of the $200.0 million milestone payment. The royalty rate applicable to any sales of OMIDRIA outside the U.S. remains unchanged at 15 percent.

● At June 30, 2023, we had $341.3 million of cash, cash equivalents and short-term investments available for operations and debt servicing along with $11.2 million of accounts receivable.

● In May 2023 we had a Type B meeting with the review division at FDA to discuss the planned resubmission of our Biologics License Application ("BLA") for narsoplimab in hematopoietic stem cell transplant-associated thrombotic microangiopathy ("TA-TMA"). Based on the agency’s feedback we expect to submit to FDA early next month a detailed plan for analysis of survival data from already-identified external sources.

● In June 2023, results from a pre-specified interim analysis of our ongoing clinical trial of OMS906 in treatment-naïve adults with paroxysmal nocturnal hemoglobinuria ("PNH") were presented at the 2023 congress of the European Hematology Association (EHA) (Free EHA Whitepaper). Statistically significant and clinically meaningful improvements were observed in all measured markers of hemolysis, including hemoglobin and lactate dehydrogenase. The OMS906 data were identified as one of the top five late-breaking submissions of the congress and were selected for presentation at a special oral session. At the end of July, we performed another analysis of the data in hand through the date of assessment. We continue to be highly encouraged by the results and plan to present the data from this most recent analysis at the upcoming congress of the American Society of Hematology (ASH) (Free ASH Whitepaper) in December.

● The Phase 2 "switch-over" trial evaluating OMS906 in patients demonstrating an unsatisfactory response to treatment with the C5 inhibitor ravulizumab is also underway. Seven of the targeted 12 patients have been enrolled with additional patients currently in screening.

"Our team continued building significant shareholder value throughout the second quarter of 2023," said Gregory A. Demopulos, M.D., Omeros’ chairman and chief executive officer. "Working with FDA, we continue to make progress toward a resubmission of our narsoplimab BLA for TA-TMA and are targeting a mid-2024 FDA decision regarding approval. As we prepare for a good outcome and subsequent market launch establishing narsoplimab as the first drug
approved for life-threatening TA-TMA, we remain on track to read out Phase 3 data later this quarter from our ARTEMIS-IGAN trial aimed at bringing narsoplimab to the large market opportunity of high-proteinuria IgA nephropathy. Our next-generation MASP-2 inhibitor, OMS1029, is in the clinic, looking well-set to be a once-quarterly subcutaneously or intravenously administered therapeutic, and is slated to begin a Phase 2 program next summer – and behind it, progressing toward the clinic, is our orally available small-molecule MASP-2 inhibitor. In the other half of our complement franchise, our Phase 2 clinical asset, OMS906, continues to deliver data consistent with a premier drug targeting the premier enzyme in the alternative pathway, increasing confidence in our objective to make OMS906 the first-line, standard-of-care for a wide range of alternative pathway disorders. At NIDA’s request and with its significant grant funding, we are advancing OMS527, our oral PDE7 inhibitor, to a Phase 2 clinical study as a treatment for cocaine use disorder and are considering assessing the drug in a Phase 2 trial for Parkinson’s-related levodopa-induced dyskinesia, a crippling unmet need affecting millions of patients. Our cellular and molecular immuno-oncology platforms also continue to mature, and we are working hard to add them to our pipeline of clinical assets. With a cash runway forecasted to fund operations well into 2025, we are strongly positioned to drive our development programs and monetize our assets. Our team’s mission is to bring transformational therapeutics to patients who need them – and that requires relentless execution against our development milestones and objectives. I’m proud of the way the Omeros team has executed in the first half of 2023, and I expect that we will continue that positive momentum into the back half of the year."

Second Quarter and Recent Clinical Developments

● Recent developments regarding narsoplimab, our lead monoclonal antibody targeting mannan-binding lectin-associated serine protease-2 ("MASP-2") in advanced clinical programs for the treatment of TA-TMA and IgA nephropathy, include:

o In May, we had a Type B meeting with FDA’s Division of Nonmalignant Hematology to discuss our planned resubmission of the BLA for narsoplimab in TA-TMA. At the meeting we received guidance from the Agency on our proposal to collect and analyze certain external survival data and to include these analyses in the BLA resubmission. Based on the Agency’s guidance, we expect to submit to FDA a detailed plan for analysis of those survival data, which are from already-identified external sources. The proposal will be submitted as a Type B meeting request, with FDA’s response expected within 60 days. After receiving FDA’s feedback on our detailed plan, we intend to conduct the analyses and, together with additional new supportive data, plan to resubmit the BLA. Assuming the full duration of relevant FDA review periods, we are targeting an approval decision by FDA in mid-2024. We expect next to provide investors with an update following BLA resubmission.

o In our Phase 3 ARTEMIS-IGAN trial evaluating narsoplimab for the treatment of IgA nephropathy, we remain on track to read out 9-month data on the proteinuria endpoint later this quarter.

o In late May, a review article authored by an international group of experts was published in Kidney International. The article describes kidney biopsies of IgA nephropathy patients, which consistently showed glomerular deposition of mannan-binding lectin together with IgA1 in up to 50% of patients with IgA nephropathy. Glomerular deposition of pattern-recognition molecules in the lectin pathway is associated with more severe glomerular damage and more severe proteinuria and hematuria. Research also suggests that lectin pathway activation contributes to tubulointerstitial fibrosis in IgA nephropathy and other proteinuric kidney disease.
● Our research efforts in COVID-19 and acute respiratory distress syndrome ("ARDS") continues at the Omeros-Cambridge Center for Complement and Inflammation Research ("OC3IR"). A manuscript detailing the beneficial effects of MASP-2 inhibition on both symptoms and survival in chemically induced ARDS was published at the end of May in Frontiers in Immunology. Another manuscript has been submitted for publication describing the pulmonary and central nervous systems benefits of MASP-2 blockade on symptoms and survival in well-established animal models of COVID-19 ARDS. Discussions are ongoing with the U.S. Government regarding development of narsoplimab for use in severe COVID-19 and other forms of ARDS.

● Recent developments regarding OMS1029, our long-acting, next-generation MASP-2 inhibitor, include:

o Dosing in a Phase 1 multiple-ascending-dose study of OMS1029 in healthy subjects was initiated on schedule in July. In a single-ascending dose Phase 1 clinical trial completed in early 2023, OMS1029 was well tolerated and no safety concerns were identified. Preliminary pharmacokinetic and pharmacodynamic ("PK/PD") data from that study showed dose-proportional exposure and sustained lectin pathway inhibition, consistent with once-quarterly intravenous or subcutaneous dosing. A Phase 2 program is slated to begin next summer.

● Recent developments regarding OMS906, our lead monoclonal antibody targeting mannan-binding lectin-associated serine protease-3 ("MASP-3"), the key activator of the alternative pathway, include:

o Enrollment is ongoing in our Phase 2 clinical trial evaluating OMS906 in PNH patients who have had an unsatisfactory response to the C5 inhibitor ravulizumab. The study has a "switch-over" design and enrolls PNH patients receiving ravulizumab, adds OMS906 to provide combination therapy with ravulizumab for 24 weeks, and then provides OMS906 monotherapy in patients who demonstrate a hemoglobin response with combination therapy. Enrollment is targeted for 12 patients, 7 of whom have already been enrolled with others in screening.

o Enrollment has been completed in the clinical trial treating patients who are not receiving complement inhibitors at entry (i.e., treatment-naïve). Data collection continues and an abstract detailing the most recent data analysis from late July has been submitted to the American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting to be held in December 2023.

o Our clinical program evaluating OMS906 in patients with complement 3 glomerulopathy ("C3G") is also underway. We are amending the dose in this trial based on data from our ongoing and completed clinical trials of OMS906 and expect soon to begin enrolling C3G patients.

o We recently engaged a group of expert hematologists for an advisory panel that yielded key insights on the current standard of care for the treatment of PNH, the unmet patient need and other factors affecting the market for PNH therapeutics. The session informed our clinical development plans and commercial strategy for OMS906 and, more generally, for our alternative pathway inhibitor program.

● Recent developments regarding OMS527, our phosphodiesterase 7 ("PDE7") inhibitor program focused on addiction and movement disorders, include:

o We continue to pursue development of our lead orally administered PDE7 inhibitor compound for the treatment of cocaine use disorder ("CUD"). This work was initiated at the request of, and is being performed in collaboration with, the National Institute on Drug Abuse ("NIDA"), part of the National Institutes of Health. The development efforts are supported by grant funding from NIDA. The three-year, $6.69 million grant is intended to support a preclinical cocaine interaction study and a randomized, placebo-controlled, inpatient clinical study evaluating the safety and effectiveness of OMS527 in patients with CUD. Previously, a Phase 1 clinical trial of the study drug in healthy subjects was successfully completed.
o Along with collaborators at Emory University we continue to evaluate the potential of our PDE7 inhibitors to treat levodopa-induced dyskinesias ("LID"). LID is caused by prolonged treatment with levodopa, the most prescribed treatment for the over 10 million patients with Parkinson’s disease worldwide. LID is reported to affect 50 percent or more of levodopa-treated patients with Parkinson’s disease. We are evaluating the data and will file patent applications as appropriate.
Financial Results

Net loss for the quarter ended June 30, 2023 was $37.3 million, or $0.59 per share. This compares to a net loss in the prior year quarter of $30.8 million, or $0.49 per share. Cash burn for the quarter ended June 30, 2023 was $30.1 million, an amount artificially inflated by $3.4 million corresponding to Rayner’s late payment of royalties received in July but due in June 2023.

For the second quarter of 2023, we earned OMIDRIA royalties of $10.7 million on Rayner’s U.S. net sales of $35.7 million. This compares to earned royalties of $17.2 million during the second quarter of the prior year on U.S. net sales of $34.5 million. The recognition of the $200 million milestone payment from Rayner in December 2022 triggered a reduction of our U.S. base royalty rate from 50 percent to 30 percent. Royalties are recorded as a reduction of the OMIDRIA contract royalty asset on our balance sheet.

Total costs and expenses for the second quarter of 2023 were $40.9 million compared to $37.4 million for the second quarter of 2022. The increase was primarily due to the advancement of our OMS906 program and incremental clinical trial costs for narsoplimab. This increase was partially offset by reductions in selling, general and administrative expenses.

Interest expense during the second quarter of 2023 was $7.9 million compared to $4.9 million during the prior year quarter. The increase was due to interest on our OMIDRIA contract royalty obligation associated with the sale of a portion of our OMIDRIA royalty receivables, which we entered into during the third quarter of 2022.

During the second quarter of 2023, we earned $4.5 million in interest and other income compared to $0.7 million in the prior year quarter. The increase was due to higher average balances available to invest and higher market interest rates in the current year quarter.

Net income from discontinued operations, net of tax, was $7.0 million, or $0.11 per share, in the second quarter of 2023 compared to $10.8 million, or $0.17 per share, in the second quarter of 2022.

As of June 30, 2023, we had $341.3 million of cash and short-term investments, all of which are held in our name, available for operations and debt service. In addition, we had $11.2 million in accounts receivable.

Conference Call Details

Omeros’ management will host a conference call and webcast to discuss the financial results and to provide an update on business activities. The call will be held today at 5:30 a.m. Pacific Time; 8:30 a.m. Eastern Time.

For online access to the live webcast of the conference call, go to Omeros’ website at View Source

To access the live conference call via phone, participants must register at this link to receive a unique PIN. Once registered, you will have two options: (1) Dial in to the conference line provided at the registration site using the PIN provided to you, or (2) choose the "Call Me" option, which will instantly dial the phone number you provide. Should you lose your PIN or registration confirmation email, simply re-register to receive a new PIN.

A replay of the call will be made accessible online at View Source