On November 12, 2020 Bicycle Therapeutics plc (NASDAQ: BCYC), a biotechnology company pioneering a new and differentiated class of therapeutics based on its proprietary bicyclic peptide (Bicycle) technology, reported that management will participate in a fireside chat at the Jefferies Virtual London Healthcare Conference on Thursday, November 19, 2020 at 1:10 p.m. ET (Press release, Bicycle Therapeutics, NOV 12, 2020, View Source [SID1234570783]).

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A live webcast of the fireside chat will be accessible in the Investors & Media section of Bicycle’s website at www.bicycletherapeutics.com. An archived replay of the webcast will be available for 90 days following the presentation date.

On November 12, 2020 eFFECTOR Therapeutics, Inc., a leader in the development of selective translation regulation inhibitors (STRIs) for the treatment of cancer, reported that the first breast cancer patient has been dosed with a combination of tomivosertib and paclitaxel in a Phase 2 study led by McGill University in Canada (Press release, eFFECTOR Therapeutics, NOV 12, 2020, View Source [SID1234570782]). The study [NCT04261218] is funded through Stand Up To Cancer (SU2C) Canada. Tomivosertib is an oral, small molecule inhibitor of MNK1/2 that enhances T cell killing of tumors, delays T cell exhaustion and enhances T cell memory. Paclitaxel is a chemotherapy agent used to treat multiple tumor types, including breast cancer.

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This Canadian study is led by Nahum Sonenberg, Ph.D., professor and Gillman Cheney Chair in biochemistry at McGill University in Montreal and a world-renowned expert in translation, and Michael Pollack, M.D., Alexander Goldfarb Research Chair in cancer research at McGill University. The Phase 2 open-label study will enroll approximately 40 patients with metastatic breast cancer for whom the standard of care has been ineffective. The study will evaluate the safety and pharmacodynamics of tomivosertib. Secondary outcomes measures include efficacy, as well as numerous biomarkers that explore the effect of tomivosertib on immune function and oncogene expression.

About Tomivosertib (eFT508)
Tomivosertib is eFFECTOR’s wholly-owned, highly selective translation regulation inhibitor that targets MNK1 and MNK2 (MNK1/2). The oral, small molecule drug candidate has been shown to enhance T cell killing, delay T cell exhaustion and enhance the T cell central memory pool. Tomivosertib is expected to enter KICKSTART, eFFECTOR’s randomized, placebo-controlled, double-blind Phase 2 study in non-small lung cancer (NSCLC) in combination with pembrolizumab, in Q4 2020. The KICKSTART study builds on results obtained in an earlier study of tomivosertib as an extension of checkpoint inhibitor treatment in patients experiencing insufficient response to an FDA-approved checkpoint inhibitor alone [NCT03616834].

Please visit www.clinicaltrials.gov for further information on ongoing clinical studies of tomivosertib.

On November 12, 2020 Eli Lilly and Company (NYSE:LLY) reported that it will participate in the Wolfe Research Virtual Healthcare Conference on Wednesday, November 18, 2020. Joshua Smiley, senior vice president and Lilly’s chief financial officer, will participate in a virtual fireside chat at 1:30 p.m., Eastern Time (Press release, Eli Lilly, NOV 12, 2020, View Source [SID1234570781]).

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A live audio webcast will be available on the "Webcasts & Presentations" section of Lilly’s Investor website at View Source A replay of the presentation will be available on this same website for approximately 90 days.

On November 12, 2020 Celyad Oncology SA (Euronext & Nasdaq: CYAD), a clinical-stage biotechnology company focused on the discovery and development of chimeric antigen receptor T cell (CAR T) therapies for cancer, reported an update on its operational developments for the third quarter ended September 30, 2020 (Press release, Celyad, NOV 12, 2020, View Source [SID1234570780]).

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"We are pleased with the continued momentum seen across our allogeneic clinical programs over the past few months," commented Filippo Petti, Chief Executive Officer of Celyad Oncology. "Major milestones during third quarter 2020 include expanding the CYAD-101 clinical program for the treatment of metastatic colorectal cancer through our recent clinical trial agreement with MSD to conduct the KEYNOTE-B79 study which will evaluate the potential synergy of pairing CYAD-101 with KEYTRUDA. We are also steadily progressing towards the initiation of the Phase 1 IMMUNICY-1 study by end of year for our anti-BCMA shRNA-based candidate CYAD-211 for the treatment of relapsed/refractory multiple myeloma. In addition, upcoming data from our autologous NKG2D receptor-based CAR T candidates, which we plan to announce at the annual ASH (Free ASH Whitepaper) congress, will help guide next steps for our AML franchise."

Third Quarter 2020 and Recent Business Highlights

Announced plans to conduct a Phase 1b KEYNOTE-B79 clinical study of non-gene edited allogeneic CAR T therapy CYAD-101 following FOLFIRI (combination of 5-fluorouracil, leucovorin and irinotecan) preconditioning chemotherapy, with MSD’s, a tradename of Merck, anti­PD-1 therapy, KEYTRUDA (pembrolizumab) in refractory metastatic colorectal cancer (mCRC) patients with microsatellite stable (MSS) / mismatch-repair proficient (pMMR) disease.
Hosted a Research & Development webinar for investors and analysts on September 29th, with a replay currently available on the Events page of the Company’s website. Topics covered during the event included:
Presentation by Dr. Richard Kim, M.D., Professor of Oncology, Moffitt Cancer Center, on the immuno-oncology and treatment landscapes for mCRC and,
Overview of Celyad Oncology’s candidate CYAD-101 for mCRC and CYAD-211 for relapsed / refractory multiple myeloma (r/r MM), and the company’s short hairpin RNA (shRNA) platform and All-in-One vector approach.
Announced U.S. Food and Drug Administration (FDA) clearance of the Investigational New Drug (IND) application and approval of the Clinical Trial Application (CTA) by the Federal Agency for Medicines and Health Products (FAMHP) of Belgium for the Company’s lead shRNA-based allogeneic candidate CYAD-211, clearing the way to initiate the Phase 1 IMMUNICY-1 clinical trial by the end of 2020.
Established an Open Market Sale AgreementSM with Jefferies LLC, pursuant to which the Company may from time to time sell through "an at the market offering" up to $25,000,000 of new American Depositary Shares.
Third Quarter 2020 Financial Review

As of September 30, 2020, the Company ended the quarter with a treasury position of €20.0 million ($23.4 million). Net cash burn during the third quarter of 2020 amounted to €6.7 million ($7.8 million), in line with expectations. The Company confirms its previous guidance that its existing treasury position should be sufficient, based on the current scope of activities, to fund operating expenses and capital expenditure requirements into the third quarter of 2021.

Update on Clinical and Preclinical Programs

CYAD-101 – Allogeneic TIM-based, NKG2D receptor-based CAR T for mCRC

Celyad Oncology’s first-in-class, non-gene edited clinical candidate CYAD-101 continues to advance in the alloSHRINK Phase 1 trial for the treatment of mCRC. CYAD-101 co-expresses the NKG2D receptor and the novel inhibitory peptide TIM (TCR Inhibitory Molecule), whose expression reduces signaling of the TCR complex by interfering with the CD3ζ component of the TCR complex. The Company plans to initiate the expansion cohort of the alloSHRINK trial which will evaluate CYAD-101 following FOLFIRI preconditioning chemotherapy in refractory mCRC patients, at the recommended dose of one billion cells per infusion. Enrollment in this expansion cohort is expected to start by year-end 2020.

Planning is also ongoing to initiate the Phase 1b KEYNOTE-B79 study of CYAD-101, following FOLFIRI preconditioning chemotherapy, with MSD’s KEYTRUDA in refractory mCRC patients with MSS / pMMR disease during the first half of 2021. The Company believes the mechanism of actions between CYAD-101 and KEYTRUDA are highly complementary and could help to drive meaningful clinical benefit in patients with advanced mCRC.

CYAD-211 – Allogeneic shRNA-based, anti-BCMA CAR T for r/r MM

CYAD-211 is an investigational, short hairpin RNA (shRNA)-based allogeneic CAR T candidate for the treatment of r/r MM. CYAD-211 is engineered to co-express a BCMA-targeting chimeric antigen receptor and a single shRNA, which interferes with the expression of the CD3ζ component of the T-cell receptor (TCR) complex. In July 2020, Celyad Oncology announced FDA clearance of its IND application for CYAD-211 and subsequently received CTA approval for CYAD-211 by the FAMHP. The Company plans to initiate the Phase 1 IMMUNICY-1 trial evaluating CYAD-211 following preconditioning chemotherapy in r/r MM by year-end 2020.

CYAD-01 – Autologous NKG2D receptor-based CAR T for r/r AML and MDS

The Company’s first-in-class NKG2D receptor-based CAR T clinical candidate CYAD-01 continues to advance in the ongoing Phase 1 THINK trial for the treatment of patients with r/r acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). The Company is scheduled to announce preliminary data from CYAD-01 produced with the OptimAb manufacturing process from the expansion cohort of the Phase 1 THINK trial at the American Society of Hematology (ASH) (Free ASH Whitepaper) conference in December 2020.

CYAD-02 – Next-Generation Autologous NKG2D receptor-based CAR T for r/r AML and MDS

CYAD-02 is an investigational CAR T therapy that engineers an All-in-One vector approach in patient’s T cells to express the NKG2D receptor CAR and shRNA to knockdown the expression of NKG2D ligands MICA and MICB on the CAR T cells. The Company is currently conducting the Phase 1 dose-escalation CYCLE-1 trial evaluating CYAD-02 for the treatment of r/r AML and MDS. During the third quarter, the Company initiated the third dose cohort of the trial. The CYCLE-1 trial is assessing the safety and clinical activity of a single infusion of CYAD-02 produced with the OptimAb manufacturing process following preconditioning chemotherapy with cyclophosphamide and fludarabine. Preliminary data from CYCLE-1 trial are expected at the ASH (Free ASH Whitepaper) conference in December 2020.

Upcoming Milestones

Plan to begin enrollment in the expansion cohort of the Phase 1 alloSHRINK trial evaluating CYAD-101 following FOLFIRI preconditioning chemotherapy in refractory mCRC patients by year-end 2020.
Expect to initiate the dose-escalation Phase 1 IMMUNICY-1 trial evaluating CYAD-211 in r/r MM by year-end 2020.
Expect to initiate the Phase 1b KEYNOTE-B79 clinical study of CYAD-101 following FOLFIRI preconditioning chemotherapy, with KEYTRUDA in refractory mCRC patients in first half of 2021.
Three abstracts accepted for presentation at the annual ASH (Free ASH Whitepaper) Meeting & Exposition, being held December 5–8, including:
Poster presentation of the Company’s anti-BCMA allogeneic CAR T candidate, CYAD-211
Poster presentations of the Company’s autologous NKG2D receptor-based CAR T candidates, CYAD-01 and CYAD-02
Upcoming Conferences

Celyad Oncology’s management team is scheduled to participate in the following conferences during the remainder of 2020:

Bryan, Garnier & Co. Virtual European Healthcare Conference, November 16, 2020
Jefferies Virtual London Healthcare Conference, November 17, 2020
SVB Leerink Oncology 1×1 Day, November 19, 2020
62nd American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting & Exposition, December 5 – 8, 2020

On November 12, 2020 Revolution Medicines, Inc. (Nasdaq: RVMD), a clinical-stage precision oncology company focused on developing targeted therapies to inhibit frontier targets in RAS-addicted cancers, reported its financial results for the third quarter and nine months ended September 30, 2020, and provided a corporate update (Press release, Revolution Medicines, NOV 12, 2020, View Source [SID1234570777]).

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"Revolution Medicines is a leader in developing innovative medicines and treatment strategies on behalf of patients with RAS-addicted tumors. We are advancing a growing portfolio consisting of both direct RAS(ON) Inhibitors and RAS Companion Inhibitors designed to enable combination approaches, including RMC-4630 targeting SHP2, RMC-5552 targeting mTORC1, and inhibitors of SOS1," said Mark A. Goldsmith, M.D., Ph.D., chief executive officer and chairman of Revolution Medicines.

"In our RAS Companion Inhibitor portfolio, we continue to make important strides with RMC-4630, our clinical stage inhibitor of SHP2. We selected the recommended Phase 2 dose and schedule (RP2DS) for both our monotherapy trial (RMC-4630-01) and the RMC-4630/cobimetinib (Cotellic) combination arm of the RMC-4630-02 clinical trial, and each trial will further evaluate the appropriate RP2DS in expansion cohorts of molecularly selected patients. As anticipated, we recently dosed a first patient in a new combination study of RMC-4630 with the third-generation EGFR inhibitor, osimertinib (Tagrisso). We also entered into a new clinical collaboration with AstraZeneca to study RMC-4630 in combination with an emerging asset targeting KRASG12C from AstraZeneca’s portfolio.

"In addition, we accelerated growth of our RAS(ON) Inhibitor platform, which has produced a collection of potent, cell-active inhibitors of diverse oncogenic RAS variants responsible for the vast majority of RAS-addicted cancers. Previously, we demonstrated significant anti-tumor effects of a representative potent and oral inhibitor of KRASG12C(ON). During the third quarter we confirmed the broad scope of our platform by demonstrating that representative KRASG12D(ON) inhibitors likewise induced tumor regressions in a preclinical model of human pancreatic cancer harboring the oncogenic KRASG12D mutation. We have advanced our KRASG12C/NRASG12C(ON), KRASG12D(ON), KRASG13C(ON) and KRASG12V(ON) inhibitor programs into lead optimization."

R&D Highlights

RAS Companion Inhibitors

Determined Recommended Phase 2 Dose and Schedule (RP2DS) for single agent RMC-4630 – Completed dose escalation and selected 200 mg administered on a Day 1/Day 2 (D1D2) weekly schedule as the RP2DS. The company plans to evaluate single agent RMC-4630 at the RP2DS in an expansion cohort of patients with gynecologic tumors harboring NF1LOF mutations, in addition to a small safety/tolerability cohort representing a broader set of histotypes and RAS pathway genotypes.

Determined RP2DS for RMC-4630 in Combination with the MEK Inhibitor, Cobimetinib – Completed dose escalation and selected RMC-4630 140 mg and cobimetinib 40 mg administered on a Day 1/Day 2 (D1D2) weekly schedule as the RP2DS. The company plans to further evaluate this combination at the RP2DS in expansion cohorts of patients with colorectal cancer harboring KRASG12V or KRASG12D mutations and others drawing from a broader set of histotypes and RAS pathway genotypes.

Interim Data Presented at ENA 2020 from Phase 1b/2 Clinical Trial Combining RMC-4630 with Cobimetinib – Interim data reported by investigators support a dual intermittent dosing strategy for RMC-4630 and cobimetinib that appears tolerable and exceeds target plasma exposures for each drug based on preclinical models of RAS pathway-driven cancers that project potential clinical activity. Investigators also reported preliminary evidence of anti-tumor activity in patients with colorectal cancer driven by KRAS mutations.

RMC-4630 Multi-Cohort Phase 1/2 Clinical Program Expanding as Potential Backbone for Combination Therapies –

Dosing and enrollment continue in the Amgen-sponsored Phase 1 study of RMC-4630 in combination with Amgen’s KRASG12C(OFF) inhibitor, AMG 510, or sotorasib
Dosing and enrollment continue in the Sanofi-sponsored Phase 1 study of RMC-4630 in combination with the PD-1 inhibitor, pembrozilumab (Keytruda)
Initiated a study evaluating RMC-4630 in combination with the EGFR inhibitor, osimertinib (Tagrisso)
Entered into a new clinical collaboration agreement with AstraZeneca to study RMC-4630 in combination with an emerging asset targeting KRASG12C from AstraZeneca’s portfolio
Clinical Results Support Dual Mechanisms of Anti-Tumor Activity by RMC-4630: Tumor Cell-Intrinsic and Stimulation of Immune Response – Data reported by the company from its ongoing RMC-4630-01 trial provide clinical evidence that SHP2 inhibition may act by stimulating arms of the immune system as a second anti-tumor mechanism in addition to its tumor cell-intrinsic benefits. These observations provide further rationale for the ongoing clinical combination study with RMC-4630 and pembrozilumab by Sanofi, the company’s SHP2 collaboration partner.
RAS(ON) Inhibitors

First-In-Class RAS(ON) Inhibitor Platform – The company’s proprietary tri-complex technology platform enables a highly differentiated approach to inhibiting RAS(ON) with potential biologic advantages. Revolution Medicines is developing a portfolio of compounds that it believes are the first and only RAS(ON) inhibitors to use this mechanism of action. The company has produced potent, cell-active RAS(ON) Inhibitors for variants driving the vast majority of RAS-addicted cancers.

Inhibitors for Five RAS(ON) Variants in Lead Optimization – KRASG12C/NRASG12C(ON), KRASG12D(ON), KRASG13C(ON), and KRASG12V(ON) inhibitors are in lead optimization, which include and expands on the company’s initial four priority RAS(ON) targets. The company remains on track to nominate a first development candidate from this platform by the end of 2020.

Preclinical Tumor Regressions Induced by First-in-Class KRASG12D(ON) Inhibitors – Data presented by the company at the RAS Targeted Drug Development conference demonstrated that the company’s first-in-class KRASG12D(ON) inhibitors induced significant decreases in tumor volume in a xenograft model of human pancreatic cancer driven by a KRASG12D mutation. The KRASG12D genotype is of particularly high clinical interest as there are currently no approved targeted therapies for the treatment of cancers driven by this mutation, which is found in approximately 35% of pancreatic cancers and 15% of colorectal cancers in the U.S.
Corporate Highlights

Completed Follow-On Financing – The company completed a follow-on equity public offering in July 2020. The upsized financing raised gross proceeds of $179.4 million before deducting underwriting discounts, commissions and other offering expenses payable by Revolution Medicines, further strengthening its balance sheet to support multiple clinical milestones and extend the company’s runway.
Upcoming Corporate Milestones

RAS(ON) Inhibitors

Nominate first development candidate (Q4 2020)
Nominate second development candidate (1H 2021)
RAS Companion Inhibitors

SHP2 (RMC-4630)
Report monotherapy dose escalation safety data set (1H 2021)
Provide preliminary activity data for combination with cobimetinib (2H 2021)
Provide initial tolerability and PK data for combination with osimertinib (2H 2021)
mTORC1/4EBP1 (RMC-5552)
Advance to IND-ready status (Q4 2020)
Begin treating patients with monotherapy (1H 2021)
Third Quarter 2020 Financial Highlights

Cash Position: Cash, cash equivalents and marketable securities were $466.1 million as of September 30, 2020, compared to $122.8 million as of December 31, 2019. The increase was primarily due to proceeds from the company’s initial public offering in February 2020 and follow-on equity public offering in July 2020.

Revenue: Total revenue, consisting of revenue from the company’s collaboration agreement with Sanofi, was $12.7 million for the quarter ended September 30, 2020, compared to $12.5 million for the quarter ended September 30, 2019.

R&D Expenses: Research and development expenses were $34.9 million for the quarter ended September 30, 2020, compared to $23.0 million for the quarter ended September 30, 2019. This increase was primarily due to an increase in research expenses associated with the company’s pre-clinical research portfolio, and an increase in personnel-related expenses related to additional headcount.

G&A Expenses: General and administrative expenses were $5.3 million for the quarter ended September 30, 2020, compared to $3.1 million for the quarter ended September 30, 2019. This increase was primarily due to an increase in expenses associated with operating as a public company.

Net Loss: Net loss was $27.2 million for the quarter ended September 30, 2020, compared to net loss of $12.8 million for the quarter ended September 30, 2019.