On November 10, 2021 Merus N.V. (Nasdaq: MRUS), a clinical-stage oncology company developing innovative, full-length multispecific antibodies (Biclonics and Triclonics), reported that Bill Lundberg, M.D., Chief Executive Officer of Merus, will participate in a fireside chat at the Jefferies London Healthcare Conference (Virtual) (Press release, Merus, NOV 10, 2021, View Source [SID1234595271]).

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The prerecorded fireside chat will be available starting on Thursday, November 18, 2021 at 8:00 am GMT/3:00 am ET on the Investors page of the Company’s website and remain available for a limited time.

On November 10, 2021 Vaccibody AS, a clinical-stage biopharmaceutical company dedicated to the discovery and development of vaccines and novel immunotherapies, reported that its Chief Executive Officer, Michael Engsig and Chief Innovation and Strategy Officer, Agnete Fredriksen, will present at Jefferies London Healthcare Conference on November 16, 2021 at 9.40 am CET and be available for 1:1 investor meetings (Press release, Vaccibody, NOV 10, 2021, View Source [SID1234595668]).

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The presentation may be viewed here: View Source

On November 10, 2021 Repare Therapeutics Inc. ("Repare" or the "Company") (Nasdaq: RPTX), a leading clinical-stage precision oncology company enabled by its proprietary synthetic lethality approach to the discovery and development of novel therapeutics, reported financial results for the third quarter ended September 30, 2021 (Press release, Repare Therapeutics, NOV 10, 2021, View Source [SID1234595054]).

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"We are pleased with the progress we’ve made this quarter in our Phase 1 part of the RP-3500 program, including the comprehensive safety data and emerging evidence of activity from the TRESR study which was part of the featured oral presentation at the AACR (Free AACR Whitepaper)-NCI-EORTC conference this year," said Lloyd M. Segal, President and Chief Executive Officer of Repare. "The findings continue to suggest RP-3500 may have broad clinical efficacy in tumors with diverse genetic alterations and provides further clinical proof of concept and validation of our SNIPRx platform. We look forward to providing updates in the future on the potential of RP-3500, both as a monotherapy and in combination with PARP inhibitors."

Third Quarter 2021 Review and Operational Updates:

Announced initial monotherapy clinical data from Phase 1/2 TRESR study of RP-3500 in patients with solid tumors at the AACR (Free AACR Whitepaper)-NCI-EORTC conference
Early data showed RP-3500 appears safe and well tolerated. The most common treatment emergent adverse events in any of the 101 patients treated, expectedly, was grade 1-2 anemia, with only 21.8% of all patients experiencing Grade 3 anemia (no Grade 4). There were no discontinuations related to RP-3500 emergent adverse events and dose interruptions, and reductions or red blood cell transfusions were infrequent on the recommended 3 days on/4 days off weekly regimen.
Recommended Phase 2 dose and schedule for further monotherapy RP-3500 evaluation was determined to be 160mg, taken weekly for 3 days on and 4 days off. This schedule assures repeated weekly exposure to RP-3500 at an efficacious dose. The Grade 3 anemia rate at this schedule overall was only 14.5%.
Antitumor activity, defined as RECIST based objective responses, was observed in patients with tumors harboring SNIPRX predicted genomic alternations at doses >100mg (ATM, CDK12, BRCA1, BRCA2, RAD51C), across multiple tumor types and included patients after PARP inhibitor failure. Meaningful clinical benefit was observed in 49% of 69 patients with available scans. Those include 12 patients with tumor responses per established international efficacy criteria, 14 patients with ongoing stable disease for at least 16 weeks and an additional 8 patients with stable disease who only had two radiological evaluations, but had demonstrated significant decreases in tumor markers or initial tumor shrinkage of less than 30%. Promising deep molecular responses in circulating tumor DNA (ctDNA) for tumors with STEP2 genomic alterations were observed in a subset of patients available for serial ctDNA analysis.
Final readouts from patients enrolled in the monotherapy arm of the TRESR trial, as well as initial data from the combination arm testing RP-3500 together with PARP inhibitors, are expected in 2022.

Raised Gross Proceeds of $101.2 Million in Upsized Follow-on Public Offering
In November 2021, the Company announced the closing of an upsized unwritten follow-on public offering yielding aggregate gross proceeds of approximately $101.2 million, or net proceeds of approximately $93.9 million, after deducting underwriting commissions and estimated offering expenses of $1.2 million payable by us. All of the shares in the offering were offered by Repare Therapeutics.
Appointed Thomas Civik to Board of Directors as new Chairman
In September 2021, the Company appointed Thomas Civik to its Board of Directors as its Chairman. He replaced Jerel Davis, Ph.D., who remains a Board member.
Mr. Civik was most recently President and CEO of Five Prime Therapeutics until its $1.9 billion acquisition by Amgen in April 2021. He has over 25 years of leadership and commercial experience at various companies including Foundation Medicine and Genentech.
Achieved $0.9 million (¥100 million) research trigger pursuant to the terms of its research services, license and collaboration agreement with Ono Pharmaceutical Co., Ltd
On October 13, 2021, upon the occurrence of a specified research trigger, the Company became eligible to receive a portion, amounting to ¥100 million ($0.9 million), of the research service payments provided for in its research services, license and collaboration agreement with Ono Pharmaceutical Co., Ltd., or Ono, ("Ono Agreement") for the research of potential product candidates targeting Polθ. Furthermore, on October 29, the Company and Ono entered into an amendment to the Ono Agreement whereby the Research Term, as defined in the Ono Agreement, was extended by one year.
Third Quarter 2021 Financial Results:

Cash and cash equivalents, restricted cash and marketable securities: Cash and cash equivalents, restricted cash and marketable securities as of September 30, 2021 were $268.2 million, exclusive of the proceeds from the follow-on public offering.
Research and development expenses, net of tax credits (Net R&D): Net R&D expenses were $25.4 million and $62.1 million for the three- and nine-month periods ended September 30, 2021, respectively, as compared to $10.1 million and $27.7 million for the three- and nine-month periods ended September 30, 2020, respectively. The increase in R&D expenses for the three and nine-month periods were primarily due to increases in development costs related to the Company’s RP-3500 and RP-6306 programs, as well as increases in personnel related expenses, including share-based compensation.
General and administrative (G&A) expenses: G&A expenses were $6.6 million and $18.6 million for the three and nine-month periods ended September 30, 2021, respectively, as compared to $4.0 million and $9.6 million for the three and nine-month periods ended September 30, 2020, respectively. The increase in G&A expenses for the three and six-month periods were due to personnel related costs, including share-based compensation, and D&O insurance which increased as a result of the Company’s IPO in June 2020.
Net loss: Net loss was $30.9 million, or $0.83 per share and $78.6 million, or $2.12 per share, in the three and nine-month periods ended September 30, 2021, respectively, and $13.8 million, or $0.37 per share and $38.2 million, or $2.63 per share in the three and nine-month periods ended September 30, 2020, respectively.
About Repare Therapeutics’ SNIPRx Platform

Repare’s SNIPRx platform is a genome-wide CRISPR-based screening approach that utilizes proprietary isogenic cell lines to identify novel and known synthetic lethal gene pairs and the corresponding patients who are most likely to benefit from the Company’s therapies based on the genetic profile of their tumors. Repare’s platform enables the development of precision therapeutics in patients whose tumors contain one or more genomic alterations identified by SNIPRx screening, in order to selectively target those tumors in patients most likely to achieve clinical benefit from resulting product candidates.

On November 10, 2021 Rain Therapeutics Inc. (NasdaqGS: RAIN), (Rain), a late-stage company developing precision oncology therapeutics, reported financial results for the third quarter and nine months ended September 30, 2021, along with an update on the company’s key developments, business operations and upcoming milestones (Press release, Rain Therapeutics, NOV 10, 2021, View Source [SID1234595086]).

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"Rain has had a number of important recent accomplishments including data presentations at various medical conferences and announcement of plans to progress our lead candidate, milademetan, into a Phase 2 trial for patients with Merkel cell carcinoma," said Avanish Vellanki, co-founder and chief executive officer of Rain. "We continue to view milademetan as having a differentiated therapeutic index and will remain focused on strategies to further enhance its value for patients with MDM2-dependent cancers."

Key Developments and Operational Updates

Phase 2 Basket Trial (MANTRA-2) of Milademetan for MDM2-Amplified Advanced Solid Tumors
Rain anticipates enrolling the first patient in its multicenter, open-label Phase 2 basket trial (MANTRA-2) this quarter, evaluating milademetan, an oral mouse double minute 2 (MDM2) inhibitor for the treatment of MDM2-amplified advanced solid tumors.
Non-Clinical Data on Milademetan Presented at IASLC 2021 (Sept. 8-14, 2021) and AACR (Free AACR Whitepaper)-NCI-EORTC ("Triple Cancer Conference") 2021 (Oct. 7-10, 2021)
Rain, in collaboration with certain research partners, presented non-clinical data on milademetan in MDM2-amplified tumors, Merkel cell carcinoma, GATA3-mutant ER+ breast cancer, and mesothelioma models.
Rain Highlights Plans for Phase 2 Trial for Milademetan in Merkel Cell Carcinoma (MANTRA-3)
On the strength of recent non-clinical data from the Dana-Farber Cancer Institute presented at the Triple Cancer Conference, Rain is now prioritizing a Phase 2 clinical trial of milademetan as monotherapy in MCC patients failing first-line checkpoint inhibitors, with a trial start anticipated in mid-2022. The Phase 2 MCC clinical trial will replace the previously planned Phase 2 clinical trial of milademetan in intimal sarcoma.
Research and Development (R&D) Day
Rain hosted a R&D Day webinar on November 9, 2021 which featured several key opinion leaders in oncology, along with members of Rain’s management team, who discussed the Company’s R&D program, as well as select clinical and preclinical data. A replay of the event is archived on the Company’s corporate website here.
Anticipated Near-term Milestones

Milademetan MDM2-Amplified Phase 2 Basket Trial (MANTRA-2)
Phase 2 trial anticipated to commence enrollment this quarter
Interim data anticipated in the second half of 2022
Milademetan MCC Phase 2 Trial (MANTRA-3)
Phase 2 trial anticipated to commence in mid-2022
Milademetan Dedifferentiated Liposarcoma Phase 3 Trial (MANTRA)
Data anticipated in 2023
RAD52 Research Program
Lead candidate selection anticipated in 2022
Third Quarter Financial Results
For the three and nine months ended September 30, 2021, Rain reported a net loss of $18.4 million and $33.4 million, respectively, as compared to a net loss of $10.4 million and $15.6 million for the same periods in 2020, respectively. Net loss per share for the three and nine months ended September 30, 2021, was $0.70 and $1.96, respectively, as compared to a net loss per share of $3.05 and $4.73 for the same periods in 2020, respectively.

R&D expenses were $15.3 million and $26.1 million for the three and nine months ended September 30, 2021, respectively, as compared to $7.9 million and $11.2 million for the same periods in 2020, respectively. The increases were primarily driven by development milestone fees to Daiichi Sankyo Co., Ltd, R&D costs for Rain’s lead candidate, milademetan, mainly for its on-going Phase 3 pivotal trial in dedifferentiated liposarcoma, as well as personnel costs. Non-cash stock-based compensation expenses included in R&D expenses were approximately $0.7 million and $1.4 million in the three and nine months ended September 30, 2021, respectively, as compared to $0.2 million and $0.4 million in the same periods in 2020, respectively.

General and administrative (G&A) expenses were $3.2 million and $7.3 million for the three and nine months ended September 30, 2021, respectively, as compared to $0.6 million and $2.3 million for the same periods in 2020, respectively. The increases were primarily due to increases in various third-party G&A costs, including legal costs, outside consulting fees and accounting and audit fees associated with maintaining compliance with exchange listing and SEC requirements as a public company, as well as personnel costs. Non-cash stock-based compensation expense included in G&A expenses were approximately $0.1 million and $0.4 million for the three and nine months ended September 30, 2021, respectively as compared to $0.1 million and $0.2 million for the same periods in 2020, respectively.

Total non-cash stock-based compensation expenses were approximately $0.8 million and $1.8 million in the three and nine months ended September 30, 2021, respectively, as compared to $0.3 million and $0.6 million for the same periods in 2020, respectively.

As of September 30, 2021, Rain had $150.1 million in cash, cash equivalents and short-term investments. Rain expects that its quarter-end cash position will provide runway to continue advancing its R&D pipeline and complete all three planned clinical trials of milademetan.

As of September 30, 2021, Rain had approximately 26.5 million shares of common stock outstanding.

The Company continues to expect its full year 2021 net cash used in operating activities to be approximately $50 million to $60 million and a projected year end cash balance of approximately $137 million to $147 million in cash, cash equivalents and short-term investments.

Third Quarter 2021 Results Conference Call and Webcast Details
The management of Rain Therapeutics will host a conference call and webcast for the investment community today, November 10, 2021, at 1:30 p.m. PT (4:30 p.m. ET). The conference call can be accessed by dialing 1 (833) 562-0127 (U.S. Toll Free) / 1 (661) 567-1105 (U.S. Toll). The passcode for the conference call is 1985710. A live webcast may be accessed by visiting the "Investors" section of the Rain Therapeutics’ website at www.rainthera.com. The call will be recorded and available for replay on the Company’s website for approximately 30 days after the call.

About Milademetan

Milademetan is a small molecule, oral inhibitor of MDM2, which is oncogenic in numerous cancers. Milademetan has already demonstrated meaningful antitumor activity in an MDM2-amplified subtype of liposarcoma (LPS) and other solid tumors in a Phase 1 clinical trial, validating a rationally-designed dosing schedule to mitigate safety concerns and widen the therapeutic window of MDM2 inhibition. Milademetan is being evaluated in an ongoing Phase 3 clinical trial in patients with LPS (MANTRA) with a planned Phase 2 tumor-agnostic basket trial in certain solid tumors (MANTRA-2) anticipated to start in the fourth quarter of 2021. Rain Therapeutics also anticipates commencing a Phase 2 clinical trial of milademetan (MANTRA-3), for the treatment of patients with Merkel cell carcinoma refractory to immune checkpoint inhibition (ICI), in mid-2022. Milademetan has received U.S. Food and Drug Administration Orphan Drug Designation for patients with LPS.

On November 10, 2021 C4 Therapeutics, Inc. (C4T) (Nasdaq: CCCC), a clinical-stage biopharmaceutical company pioneering a new class of small-molecule medicines that selectively destroy disease-causing proteins through degradation, reported business highlights and financial results for the third quarter of 2021 (Press release, C4 Therapeutics, NOV 10, 2021, View Source [SID1234595103]).

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"In recent months, C4T has built momentum across our portfolio of highly potent targeted protein degraders by continuing to enroll patients in our CFT7455 Phase 1/2 clinical trial and successfully nominating our next development candidate, CFT1946, a BRAF V600X degrader for the treatment of V600 mutant solid tumors" said Andrew Hirsch, chief executive officer of C4 Therapeutics. "We remain on track to achieve our remaining 2021 milestones, including IND submission for CFT8634 and advancing our EGFR and BRAF degraders towards the clinic. Our strong balance sheet and commitment to bringing innovative treatments to patients keep us on track to deliver clinical data for CFT7455 next year and achieve four clinical programs by end of 2022."

THIRD QUARTER 2021 AND RECENT BUSINESS HIGHLIGHTS

CFT7455: CFT7455 is an orally bioavailable MonoDAC degrader targeting IKZF1/3 for the treatment of multiple myeloma and non-Hodgkin’s lymphomas, including peripheral T-cell lymphoma and mantle cell lymphoma.

Accepted to Present at the 63rd American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting & Exposition: Jesus G. Berdeja, M.D., director, multiple myeloma research at Sarah Cannon Research Institute, will present a trial-in-progress poster titled "A Phase 1 Study of CFT7455, a Novel Degrader of IKZF1/3, in Multiple Myeloma and Non-Hodgkin Lymphoma" at the ASH (Free ASH Whitepaper) Annual Meeting at 5:30 p.m. ET on Saturday, December 11, 2021. The November online supplemental issue of Blood also features the abstract.
Received Orphan Drug Designation: In August 2021, the U.S. Food and Drug Administration granted Orphan Drug Designation to CFT7455 for the treatment of multiple myeloma.
CFT8634: CFT8634 is an orally bioavailable BiDAC degrader targeting BRD9 for the treatment of synovial sarcoma and SMARCB1-null solid tumors.

Presented at the 4th Annual Targeted Protein Degradation Summit: In October 2021, C4T delivered a presentation describing the multiparameter optimization of a series of BRD9 degraders, which led to the identification of a degrader with a sufficient intravenous pharmacokinetic (PK) profile to enable in vivo proof-of-concept studies. This work served as a launching point for further optimization and eventually led to the discovery of CFT8634, an orally bioavailable BiDAC degrader targeting BRD9 for the treatment of synovial sarcoma and SMARCB1-null solid tumors.
CFT8919: CFT8919 is a potent and selective BiDAC degrader of EGFR L858R for the treatment of non-small cell lung cancer (NSCLC).

Presented at the 4th Annual Targeted Protein Degradation Summit: In October 2021, C4T delivered an encore presentation of the Company’s June presentation at the Keystone Symposium on targeted protein degradation. The presentation included pre-clinical data demonstrating CFT8919 is active in in vitro and in vivo models of acquired resistance to approved EGFR inhibitors which harbor resistance-causing secondary mutations in EGFR.
CFT1946: CFT1946 is an orally bioavailable, mutant-selective BiDAC degrader targeting BRAF V600X.

Nominated CFT1946 for Clinical Development: In August 2021, C4T and Roche selected CFT1946, a mutant-selective degrader of BRAF V600X active preclinically in the setting of acquired resistance to BRAF inhibitors, as a development candidate. C4T has initiated IND-enabling activities for CFT1946.
Regained Rights to BRAF Program from Roche: In November 2021, C4T and Roche mutually agreed to terminate their agreement solely with respect to the BRAF target, allowing C4T to advance CFT1946 and any other BRAF degraders independently from Roche. There is no impact to cash runway guidance as a result of this change. With this mutual agreement, C4T wholly owns the BRAF program and no longer has future financial obligations to Roche related to this program.
Research and Development Activities

Pre-clinical Research Paper Published in ACS Chemical Biology: In September 2021, ACS Chemical Biology featured a scientific publication from C4T titled, "Structural Characterization of Degrader-Induced Ternary Complexes Using Hydrogen–Deuterium Exchange Mass Spectrometry (HDX-MS) and Computational Modeling: Implications for Structure-Based Design." The publication describes the potential utility of HDX-MS to provide rapidly accessible structural insights into degrader-induced protein–protein interfaces in solution, and supports predictive capabilities of the TORPEDO platform.
UPCOMING KEY MILESTONES

C4T continues to advance its portfolio and is on-track to achieve four clinical programs by year-end 2022. To achieve this objective, C4T is focused on accomplishing the following activities:

Advance its CFT7455 program and share safety and efficacy data at a medical meeting in 2022.
Submit an IND application for CFT8634 by year-end 2021.
Submit an IND application for CFT8919 in mid-2022.
Submit an IND application for CFT1946 in 2022.
Continue lead optimization activities for the RET program through 2021.
UPCOMING EVENTS

November 18, 2021 – C4T will participate in the Jefferies Global Healthcare Conference.
December 2, 2021 – C4T will participate in the Evercore ISI 4th Annual HealthCONx Conference.
December 11-14, 2021 – C4T will participate in the 63rd American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting & Exposition, including the presentation of a trial-in-progress poster for CFT7455.
THIRD QUARTER 2021 FINANCIAL RESULTS

Revenue: Total revenue for the third quarter of 2021 was $8.5 million, compared to $8.4 million for the third quarter of 2020. Total revenue reflects revenue recognized under collaboration agreements with Roche, Biogen and Calico.

Research and Development (R&D) Expense: R&D expense for the third quarter of 2021 was $24.3 million, compared to $23.9 million for the third quarter of 2020. The increase in R&D expense was primarily attributable to higher pre-clinical costs related to our lead programs, and increased workforce expenses to support continued clinical development activities for CFT7455.

General and Administrative (G&A) Expense: G&A expense for the third quarter of 2021 was $8.5 million, compared to $2.9 million for the third quarter of 2020. The increase in G&A expense was primarily attributable to an increase in stock-based compensation expense, which was driven by new stock option grants and a higher fair value of those stock options, as well as higher professional fees and insurance costs resulting from our transition to a public company.

Net Loss and Net Loss per Share: Net loss for the third quarter of 2021 was $24.7 million, compared to $21.8 million for the third quarter of 2020. Net loss per share for the third quarter of 2021 was $0.51, compared to $17.55 for the third quarter of 2020. The decrease in net loss per share, despite the increase in net loss, was driven by a significant increase in the weighted-average number of shares outstanding. This increase in shares outstanding was caused by our initial public offering of 11,040,000 common shares in October 2020 and the resultant conversion of then outstanding shares of redeemable convertible preferred stock into 30,355,379 shares of common stock, together with our issuance of 4,887,500 shares of common stock upon the closing of our follow-on offering in June 2021.

Cash Position and Financial Guidance: Cash, cash equivalents and marketable securities as of September 30, 2021 were $480.3 million, compared to $371.7 million as of December 31, 2020. The change in cash was primarily driven by net proceeds from our June 2021 follow-on offering of $169.5 million, offset by expenditures to fund operations. C4T expects that our cash, cash equivalents and marketable securities as of September 30, 2021, together with future payments expected to be received under existing collaboration agreements, will be sufficient to fund planned operating expenses and capital expenditures for at least the next 24 months.