On August 8, 2023 Monopar Therapeutics Inc. (Nasdaq: MNPR), a clinical-stage biopharmaceutical company focused on developing innovative treatments for cancer, reported an update from its currently enrolling multi-center open-label Phase 1b clinical trial of camsirubicin in patients with advanced soft tissue sarcoma (ASTS) (Press release, Monopar Therapeutics, AUG 8, 2023, View Source [SID1234634008]). Both patients treated to date at the 650 mg/m2 dose level have experienced tumor size reductions – of 18% and 20% respectively – after the first two cycles of camsirubicin treatment. Both patients are set to receive additional cycles of camsirubicin treatment, as well, which may result in further tumor size reduction.

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The Phase 1b clinical trial data is continuing to support Monopar’s dose-response hypothesis with camsirubicin. The best response seen prior to the current 650 mg/m2 dose level was at the immediately prior dose level (520 mg/m2), which was a 21% reduction in tumor size in a patient after receiving six cycles of camsirubicin treatment. This patient’s cancer was unresectable at study entry, but after the tumor size reduction, became eligible and the patient underwent successful surgical removal of their cancer with clear margins. Furthermore, all three patients at the 520 mg/m2 dose level achieved stable disease and had either a net reduction or no overall change in tumor size per RECIST 1.1 while on study drug.

Additionally, no drug­related cardiotoxicity has been observed in the trial to date as evaluated by the industry standard left ventricular ejection fraction (LVEF), and no toxicities have been experienced by any patient that have required expanding the size of a dose cohort. Further, 71% of camsirubicin patients have experienced no hair loss, and only approximately 14% have experienced >50% hair loss, with the remainder having low grade hair loss. This compares favorably to the approximately 50% of doxorubicin treated patients in recent ASTS clinical trials reporting some amount of hair loss, with the majority of these patients experiencing >50% hair loss. Only 14% of camsirubicin patients in the Phase 1b trial have experienced mild-to-severe oral mucositis. This compares favorably to the roughly 35-40% of doxorubicin-treated patients in recent ASTS clinical trials that experienced mild-to-severe oral mucositis.

ASTS is a deadly cancer with inadequate treatment options. Doxorubicin is currently the first-line standard of care treatment for most types of ASTS, and the average life expectancy from time of diagnosis for these patients is only about 12 to 15 months. Because of the risk of irreversible heart damage, patients discontinue doxorubicin treatment after just 6 to 8 cycles. Camsirubicin has been designed to retain the anti-cancer activity while avoiding the irreversible heart damage that is seen with doxorubicin. The value-driving hypothesis for camsirubicin is straightforward: modifying doxorubicin in order to reduce cardiac damage could enable higher and longer dosing, resulting in better efficacy and patient outcomes.

Camsirubicin Clinical Trial Design and GEIS Collaboration

The purpose of this dose escalation Phase 1b trial is to determine the maximum tolerated dose (MTD) of camsirubicin. Once the MTD is reached, Monopar has a clinical collaboration agreement in place with the Spanish Sarcoma Group (Grupo Español de Investigación en Sarcomas, or GEIS) to conduct a multi-country randomized Phase 2 clinical trial. The Phase 2 plan is to evaluate camsirubicin head-to-head against doxorubicin in patients with ASTS, with GEIS as the study sponsor with support from Monopar.

Further information about this actively enrolling, open-label, dose-escalation Phase 1b clinical trial is available at www.ClinicalTrials.gov under study identifier NCT 05043649.

On August 8, 2023 iTeos Therapeutics, Inc. (Nasdaq: ITOS), a clinical-stage biopharmaceutical company pioneering the discovery and development of a new generation of immuno-oncology therapeutics for patients, reported financial results for the second quarter ended June 30, 2023 and provided a business update (Press release, iTeos Therapeutics, AUG 8, 2023, View Source [SID1234634007]).

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"Our team continues to bring forward innovation in immunotherapy through our differentiated development pipeline, which is expected to make significant progress in the second half of 2023," said Michel Detheux, Ph.D., president and chief executive officer of iTeos. "To start, with GSK’s anti-PD-1 mAb, dostarlimab, as the backbone for our ambitious TIGIT-based clinical development plans, we remain confident that its combination with belrestotug has the potential to become a best-in-class program. Furthermore, we are continuing to build our position as a leader unlocking the adenosine pathway with the announcement of enrolling patients in the Phase 1 trial of EOS-984. This program will deepen our understanding of the mechanisms of adenosine-mediated immunosuppression and potentially reinforce the unique, insurmountable profile of inupadenant. Based on the progression of our 9 ongoing clinical trials and solid cash position with runway into 2026, we believe we are poised for an abundance of opportunity in 2024, including the presentation of TIGIT data from the Phase 2 clinical trials treating patients with NSCLC and HNSCC."

Program Highlights:

Belrestotug (EOS-448/GSK4428859A): IgG1 anti-TIGIT monoclonal antibody designed to
engage the Fc gamma receptor (FcγR) and enhance the anti-tumor response through multifaceted mechanisms.

In collaboration with GSK, late-stage development of belrestotug as a potential next-generation immuno-oncology (IO) agent through multiple combination studies are progressing as expected. We plan to present related datasets in 2024. Preparation is underway for Phase 3 registrational studies evaluating belrestotug and dostarlimab combination.
The ongoing trials include:
Randomized Phase 2 trial assessing the doublet of dostarlimab with belrestotug in previously untreated advanced / metastatic non-small cell lung cancer (NSCLC).
Phase 2 expansion study assessing the doublet of dostarlimab with belrestotug in first line advanced or metastatic head and neck squamous cell carcinoma (HNSCC).
Phase 1b trials exploring the addition of chemotherapy and two novel triplets in selected advanced solid tumors: belrestotug with dostarlimab and GSK’s investigational anti-CD96 antibody, and belrestotug with dostarlimab and GSK’s investigational anti-PVRIG antibody.
Additional studies include the continued advancement of the monotherapy dose escalation part of a Phase 1/2 trial evaluating belrestotug as both a monotherapy and in combination with Bristol Myers Squibb’s iberdomide in multiple myeloma.
Adenosine Pathway

Inupadenant (EOS-850): Designed as an insurmountable and highly selective small molecule antagonist of the adenosine A2A receptor, the only high-affinity adenosine receptor expressed on multiple immune cells found in the tumor microenvironment. Highlights include:

Progression of the ongoing two-part Phase 2 trial in post-IO metastatic non-squamous NSCLC to evaluate the combination of inupadenant with platinum-doublet chemotherapy compared to standard platinum-doublet chemotherapy.
EOS-984: First-in-class small molecule program targeting a novel mechanism in the adenosine pathway.

The company has initiated enrolling patients in its Phase 1 trial of EOS-984.
This complementary clinical development program has the potential to fully reverse the profound immunosuppressive action of adenosine on T and B cells. EOS-984’s effects have been shown preclinically to be enhanced by combining with inupadenant and other standards of care.
Second Quarter 2023 Financial Results

Cash and Investment Position: The company’s cash, cash equivalents, and investments position was $677.5 million as of June 30, 2023, as compared to $791.9 million as of June 30, 2022. The company continues to expect its cash balance to provide runway into 2026.
Research and Development (R&D) Expenses: R&D expenses were $29.2 million and $54.9 million for the quarter and six months ended June 30, 2023, respectively, as compared to $26.9 and $48.0 million for the same quarter and six months of 2022, respectively. The increases in each comparative period were primarily due to increases in activities related to the belrestotug, inupadenant, and EOS-984 programs.
General and Administrative (G&A) Expenses: G&A expenses were $13.4 million and $25.4 million for the quarter and six months ended June 30, 2023, respectively, as compared to $11.5 million and $22.1 million for the same quarter and six months of 2022, respectively. The increases were primarily due to increases in headcount and related costs compared to the same quarter and six months last year.
Net Income/Loss: Net loss attributable to common shareholders was $34.3 million, or net loss of $0.96 per basic and diluted share for the quarter ended June 30, 2023, as compared to a net income of $5.6 million, or a net income of $0.16 per basic share and $0.15 per diluted share for the same quarter of 2022. Net loss attributable to common shareholders was $49.9 million, or net loss of $1.39 per basic and diluted share for the six months ended June 30, 2023, as compared to a net income of $75.2 million, or a net income of $2.12 per basic share and $1.98 per diluted share for the same six months of 2022.

On August 8, 2023 Plus Therapeutics, Inc. (Nasdaq: PSTV) (the "Company"), a clinical-stage pharmaceutical company developing targeted radiotherapeutics with advanced platform technologies for central nervous system cancers, reported a key opinion leader roundtable discussion to be held on Friday, August 11, 2023, 8:00 a.m. – 9:00 a.m. ET to discuss the latest data from the ReSPECT-LM clinical trial of rhenium (186Re) obisbemeda that will be presented at the Society for Neuro Oncology (SNO)/American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Central Nervous System (CNS) Cancer Conference on August 10, 2023 (Press release, PLUS THERAPEUTICS, AUG 8, 2023, View Source;_hsmi=269509104&_hsenc=p2ANqtz-89_OBvNFnW0uugglRG4wRRBcKdiDIT1INGLN7Tn-CIPCJ9ScMxixrB48kxKd8Uu3vpBKS9BMOI04QHVJaIree6xQ-Bfw&utm_content=269509104&utm_source=hs_email [SID1234634006]).

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The webinar will feature a comprehensive discussion about the ongoing ReSPECT-LM Phase 1/2a dose escalation clinical trial, including key safety, tolerability, dosing, feasibility and efficacy data. Speakers include:

Andrew J. Brenner, M.D., Ph.D., Professor of Medicine, Neurology, and Neurosurgery at The University of Texas, Health Services Center at San Antonio and principal investigator of the ReSPECT-GBM trial and co-principal investigator of the ReSPECT-LM trial.
Priya Kumthekar, M.D., Associate Professor of Neurology and Medicine (Hematology and Oncology) at Northwestern University’s Feinberg School of Medicine and co-principal investigator of the ReSPECT-LM trial.
Marc H. Hedrick, M.D., President and Chief Executive Officer of Plus Therapeutics
Justin Walsh, Ph.D., Senior Healthcare Analyst, Jones Research will moderate the roundtable and in addition will provide an overview of the radiotherapeutic market.
Webcast Details

A webinar with accompanying slides will be available in the Events page of the Investor Relations section of the Plus Therapeutics website beginning Friday, August 11, 2023 at 8:00 a.m. ET. Participants may also pre-register any time before the call here. Please access the webinar 15 minutes prior to the start time.

The webinar will be available on the Company’s website under the ‘For Investor’ section. The webcast will be available on the Company’s website for 90 days following the live call.

On August 8, 2023 Mirati Therapeutics, Inc. (Nasdaq: MRTX), a commercial stage biotechnology company, reported that it intends to offer and sell $250.0 million of shares of its common stock, and, to certain investors, pre-funded warrants to purchase shares of common stock, in an underwritten public offering (Press release, Mirati, AUG 8, 2023, View Source [SID1234634005]). The purchase price of each pre-funded warrant will equal the price per share at which shares of common stock are being sold to the public in this offering, minus $0.001, which will be the per share exercise price of each pre-funded warrant. In addition, Mirati expects to grant the underwriters of the offering a 30-day option to purchase up to an additional $37.5 million of shares at the public offering price, less the underwriting discounts and commissions. The offering is subject to market and other conditions, and there can be no assurance as to whether or when the offering may be completed, or as to the actual size or terms of the offering.

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Goldman Sachs & Co. LLC is acting as the book-running manager for the proposed offering. Leerink Partners LLC is acting as financial advisor for the proposed offering.

The securities described above are being offered pursuant to a shelf registration statement filed by Mirati with the Securities and Exchange Commission ("SEC") that became automatically effective upon filing. A preliminary prospectus supplement and accompanying prospectus relating to the offering will be filed with the SEC and will be available on the SEC’s website located at View Source Copies of the preliminary prospectus supplement and the accompanying prospectus relating to the offering, when available, may be obtained from Goldman Sachs & Co. LLC, Attention: Prospectus Department, 200 West Street, New York, New York 10282, by telephone at (866) 471-2526, or by email at [email protected].

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

On August 8, 2023 Verastem Oncology (Nasdaq: VSTM), a biopharmaceutical company committed to advancing new medicines for patients with cancer, reported financial results for the second quarter ending June 30, 2023 and highlighted recent progress (Press release, Verastem, AUG 8, 2023, View Source [SID1234634004]).

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"We made significant advancements in the second quarter, including presenting positive results from the RAMP 201 trial of avutometinib and defactinib in recurrent LGSOC and finalizing the design of the confirmatory Phase 3 trial. Both are important milestones in our plan to file for accelerated approval in LGSOC based on mature results from RAMP 201 and data from the investigator sponsored FRAME trial," said Dan Paterson, President and Chief Executive Officer, Verastem Oncology. "Our work to strengthen our balance sheet will enable our continued progress across our RAMP programs in LGSOC, non-small lung cancer and pancreatic cancer and support continued preparation for a potential commercial launch in LGSOC. We are encouraged by the progress we have made and believe we are well positioned to address significant unmet needs in RAS pathway-driven cancers."

Second Quarter 2023 and Recent Highlights

Low Grade Serous Ovarian Cancer (LGSOC)

The Company finalized the design of the Phase 3 confirmatory trial (RAMP 301) of avutometinib and defactinib in LGSOC versus standard of care (SOC) chemotherapy (pegylated liposomal doxorubicin, paclitaxel, topotecan) or hormone therapy (letrozole, anastrozole). RAMP 301 is an international collaboration between The GOG Foundation, Inc. (GOG) and the European Network of Gynaecological Oncological Trial groups (ENGOT) sponsored by Verastem Oncology. The trial will enroll approximately 270 patients who will be randomized to either the combination of avutometinib and defactinib or SOC. The primary endpoint is progression free survival (PFS) by blinded independent central review (BICR). Secondary endpoints include overall response rates, duration of response, disease control rate, safety and tolerability, patient reported outcomes and overall survival.
RAMP 301 is the follow-up confirmatory study being conducted for full regulatory approval in recurrent LGSOC. The Company intends to file for accelerated approval with the U.S. Food and Drug Administration (FDA) for the combination of avutometinib and defactinib based on mature data from the Company’s Phase 2 registration-directed trial, RAMP 201, together with the results of the investigator-initiated FRAME trial.
Data from Part A of the RAMP 201 trial were presented at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Meeting in June. Results included confirmed objective response rates (ORR) by BICR of 45% (13/29; 95% CI: 26%-64%).​ Overall, patients were heavily pretreated with a median of 4 prior systemic regimens (up to 11). Tumor shrinkage was observed in the majority of patients, 86% (25/29). The safety profile was tolerable and consistent with previously reported safety data. These results are consistent with the data that supported the Breakthrough Therapy Designation granted by the FDA for the combination in recurrent LGSOC after one or more prior lines of therapy, including platinum-based chemotherapy.
Other Programs

In the Company’s RAMP 203 and RAMP 204 Phase 1/2 clinical trials, the combinations of avutometinib with Amgen’s LUMAKRAS (sotorasib) (RAMP 203) and with Mirati’s KRAZATI (adagrasib) (RAMP 204) are evaluated in patients with KRAS G12C mutant non-small cell lung cancer (NSCLC). RAMP 203 progressed to the recommendation of the Phase 2 dose (avutometinib 4 mg BIW PO and sotorasib 960 mg QD PO) and continues enrollment in Part B dose expansion in patients who are G12C inhibitor treatment naïve and in patients who experienced disease progression on prior G12C inhibitor monotherapy. Dose escalation is ongoing in RAMP 204.
Enrollment is ongoing in the Company’s RAMP 205 Phase 1b/2 clinical trial evaluating avutometinib and defactinib in combination with SOC chemotherapy (GEMZAR (gemcitabine) and ABRAXANE) in patients with metastatic adenocarcinoma of the pancreas. The trial is supported by the Company’s receipt of the first "Therapeutic Accelerator Award" from the Pancreatic Cancer Action Network (PanCAN).
Corporate Updates

Dan Paterson was promoted to President and Chief Executive Officer in July. During his tenure as President and Chief Operating Officer of Verastem Oncology, he spearheaded the acquisition of lead compound avutometinib and led strategic direction designed to accelerate the program’s advancement. In connection with his appointment, Dan was also appointed to the Board of Directors. Dan succeeds Brian Stuglik who has retired from his role as Chief Executive Officer but remains a member of the Company’s Board of Directors and leads the Board’s recently designated Commercialization Committee.
The Company strengthened the balance sheet in June 2023 by raising gross proceeds of approximately $97.8 million in a public offering of 8,489,409 shares of common stock and, in lieu of common stock to certain investors, pre-funded warrants to purchase an aggregate of 1,538,591 shares of common stock.
Karin Tollefson was elected to Verastem Oncology’s Board of Directors at the Company’s annual meeting, alongside returning Board members Robert Gagnon and Brian Stuglik. Dr. Tollefson is the Senior Vice President and Head of Global Medical Affairs at Seagen Inc. Karin has 30 years of experience in the pharmaceutical industry and is a proven leader in global oncology development and medical affairs.
Second Quarter 2023 Financial Results

Verastem Oncology ended the second quarter of 2023 with cash, cash equivalents and investments of $183.1 million. Total operating expenses for the three months ended June 30, 2023 (the "2023 Quarter") were $20.3 million, compared to $21.4 million for the three months ended June 30, 2022 (the "2022 Quarter"). Recent historical operating expenses have ranged between $16.0M and $20.0M per quarter, which the Company does not anticipate will change significantly in the near term as the RAMP 301 trial commences.

Research & development expenses for the 2023 Quarter were $12.9 million, compared to $14.9 million for the 2022 Quarter. The decrease of $2.0 million, or 13.4%, primarily resulted from a decrease in drug product and drug substance costs and contract research organization costs.

Selling, general & administrative expenses for the 2023 Quarter were $7.4 million, compared to $6.5 million for the 2022 Quarter. The increase of $0.9 million, or 13.8%, was primarily related to increased consulting and professional fees as well as additional costs in anticipation of a potential launch of avutometinib and defactinib in LGSOC.

Net loss for the 2023 Quarter was $24.3 million, or $1.37 per share (basic and diluted, each as adjusted for the Company’s reverse stock split), compared to net loss of $22.0 million, or $1.41 per share (basic and diluted, each as adjusted for the Company’s reverse stock split) for the 2022 Quarter.

For the 2023 Quarter, non-GAAP adjusted net loss was $18.8 million, or $1.06 per share (diluted, as adjusted for the Company’s reverse stock split), compared to non-GAAP adjusted net loss of $20.1 million, or $1.29 per share (diluted, as adjusted for the Company’s reverse stock split) for the 2022 Quarter. Please refer to the GAAP to Non-GAAP Reconciliation attached to this press release.

Use of Non-GAAP Financial Measures

To supplement Verastem Oncology’s condensed consolidated financial statements, which are prepared and presented in accordance with generally accepted accounting principles in the United States (GAAP), the Company uses the following non-GAAP financial measures in this press release: non-GAAP adjusted net loss and non-GAAP adjusted net loss per share. These non-GAAP financial measures exclude certain amounts or expenses from the corresponding financial measures determined in accordance with GAAP. Management believes this non-GAAP information is useful for investors, taken in conjunction with the Company’s GAAP financial statements, because it provides greater transparency and period-over-period comparability with respect to the Company’s operating performance and can enhance investors’ ability to identify operating trends in the Company’s business. Management uses these measures, among other factors, to assess and analyze operational results and trends and to make financial and operational decisions. Non-GAAP information is not prepared under a comprehensive set of accounting rules and should only be used to supplement an understanding of the Company’s operating results as reported under GAAP, not in isolation or as a substitute for, or superior to, financial information prepared and presented in accordance with GAAP. In addition, these non-GAAP financial measures are unlikely to be comparable with non-GAAP information provided by other companies. The determination of the amounts that are excluded from non-GAAP financial measures is a matter of management judgment and depends upon, among other factors, the nature of the underlying expense or income amounts. Reconciliations between these non-GAAP financial measures and the most comparable GAAP financial measures for the three and six months ended June 30, 2023, and 2022 are included in the tables accompanying this press release, after the unaudited condensed consolidated financial statements.

About Avutometinib (VS-6766)

Avutometinib is a RAF/MEK clamp that induces inactive complexes of MEK with ARAF, BRAF and CRAF potentially creating a more complete and durable anti-tumor response through maximal RAS pathway inhibition. Avutometinib is currently in late-stage development.

In contrast to other MEK inhibitors, avutometinib blocks both MEK kinase activity and the ability of RAF to phosphorylate MEK. This unique mechanism allows avutometinib to block MEK signaling without the compensatory activation of MEK that appears to limit the efficacy of other inhibitors. The U.S. Food and Drug Administration granted Breakthrough Therapy designation for the combination of Verastem Oncology’s investigational RAF/MEK clamp avutometinib, with defactinib, its FAK inhibitor, for the treatment of all patients with recurrent low-grade serous ovarian cancer (LGSOC) regardless of KRAS status after one or more prior lines of therapy, including platinum-based chemotherapy.

Verastem Oncology is currently conducting clinical trials with its RAF/MEK clamp avutometinib in RAS- driven tumors as part of its (Raf And Mek Program). RAMP 201 is a registration-directed trial of avutometinib in combination with defactinib in patients with recurrent LGSOC. Verastem Oncology has established clinical collaborations with Amgen and Mirati to evaluate LUMAKRAS (sotorasib) and KRAZATI (adagrasib) in combination with avutometinib in KRAS G12C mutant NSCLC as part of the RAMP 203 and RAMP 204 trials, respectively. As part of the "Therapeutic Accelerator Award" Verastem Oncology received from PanCAN, Verastem Oncology is conducting RAMP 205, a Phase 1b/2 clinical trial evaluating avutometinib and defactinib with gemcitabine/nab-paclitaxel in patients with front-line metastatic pancreatic cancer.