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Anticancer Bioscience Announces Preclinical Data of Lead Compounds Against Novel Myc Synthetic Lethal Target in Cancer

On May 11, 2021 Anticancer Bioscience (ACB), pioneers in synthetic lethal approaches to precision oncology, reported that progress in its MYC-synthetic lethal (MYC-SL) program (Press release, Anticancer Bioscience, MAY 11, 2021, View Source [SID1234579676]). The Company has identified three classes of novel small molecule compounds that demonstrate robust anti-cancer activity in preclinical studies, acting through interfering with mitosis and blocking cytokinesis. ACB is progressing through optimization and final candidate selection with the goal of progressing at least one of these MYC-SL compounds into clinical trials by 2022.

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The MYC family oncogene, encoding a transcription factor Myc, is deregulated in over 50% of human cancers, and this deregulation is frequently associated with poor prognosis and unfavorable patient survival. Myc has a central role in almost every aspect of the oncogenic process, orchestrating proliferation, apoptosis, differentiation, and metabolism. Direct targeting of Myc has been a challenge for decades owing to its "undruggable" protein structure, with a lack of a drug binding pocket. The synthetic lethality associated with Myc overexpression is being explored for its potential in the development of novel anti-cancer therapies.

Commenting on the progress and pre-clinical data, Dun Yang PhD, Founder, President, and CEO of ACB said:

"We are excited by our early in vitro and in vivo pre-clinical studies and in our molecular biology work to identify the target that our novel compounds hit. In animal models, data consistent with the in vitro studies has confirmed that the MYC-SL compounds act through interfering mitosis and blocking cytokinesis. We have filed patents on our compounds and are progressing rapidly through optimization to candidate selection and IND enabling studies."

The novel target for ACB’s MYC-SL compounds has been identified and will be subject to peer review publication in due course.

ACB has developed an innovative and proprietary general utility new scaffold-drug fragment (GUNS-DF) library approach to small molecule drug discovery. It is constructing 10 types of pilot GUNS-DF libraries, each of which contains a distinct core scaffold. Twenty compounds with excellent drug-like properties have been identified from three types of GUNS-DF libraries with a potency of less than 20 nM in a cell-based assay for MYC-SL agents. This potency was achieved after synthesizing and screening approximately 350 analogs during lead optimization.

At low nM concentrations, these compounds elicited potent cytotoxicity in a panel of 50 cell lines representing a variety of human malignancies. With adequate bioavailability, many of these compounds also suppressed the growth of various cancer cell lines that grew as xenografts in immunocompromised mice.

Having raised CNY131m (~USD21m) in seed finance to fund its discovery research, ACB is currently pursuing a Series A financing to progress at least one of its MYC-SL compounds into clinical trials.

ACB will be showcasing its innovative drug discovery platforms and pipeline at ChinaBio and BioEquity in May, and at BIO in June.

Ipsen opts-in to join Exelixis with ongoing development of Cabometyx® for people living with a form of thyroid cancer, based on promising interim results

On May 11, 2021 Ipsen (Euronext: IPN; ADR: IPSEY) reported it has exercised its option to collaborate with Exelixis, Inc. (Exelixis) in the pivotal COSMIC-311 Phase III trial (Press release, Ipsen, MAY 11, 2021, View Source [SID1234579675]). COSMIC-311 is evaluating Cabometyx (cabozantinib) 60 mg versus placebo in people living with radioiodine-refractory differentiated thyroid cancer (DTC) who have progressed after up to two prior vascular endothelial growth factor receptor (VEGFR)-targeted therapies.2 Radioactive iodine (RAI) is a treatment option for DTC when patients are at high risk of disease recurrence, have incompletely resected cancer, or distant metastases.3 Patients who develop RAI-refractory DTC, whereby they are resistant to RAI treatment, typically have a poor prognosis with an estimated survival of three to five years on average.4

Howard Mayer, Executive Vice President and Head of Research and Development at Ipsen, commented:
"A planned interim analysis of the COSMIC-311 Phase III trial has shown promising and clinically meaningful results in the use of Cabometyx in people living with radioiodine-refractory differentiated thyroid cancer who have progressed after prior therapy. We are delighted to build on our strong foundation and join Exelixis to further evaluate, and to work with regulatory authorities on, the potential of Cabometyx in a patient population who currently have limited treatment options."

Results from the planned Phase III interim analysis of COSMIC-311 showed that the trial met the co-primary endpoint of demonstrating significant improvement in progression-free survival.1 The detailed results from the analysis will be presented at the forthcoming ASCO (Free ASCO Whitepaper) Annual Meeting, taking place virtually from 4 to 8 June 2021.

Ipsen has an exclusive collaboration agreement with Exelixis for the commercialization of Cabometyx outside of the U.S. and Japan. Following the decision to opt-in to the COSMIC-311 trial, Ipsen gains access to the results to support potential future regulatory submissions in its territories.

The U.S. Food and Drug Administration (FDA) granted Breakthrough Therapy Designation for Cabometyx in February 2021 as a potential treatment for people living with DTC who have progressed following prior therapy and who are RAI-refractory (if RAI is appropriate).

Pulmatrix Reports First Quarter 2021 Financial Results and Provides Business Update

On May 11, 2021 Pulmatrix, Inc. (NASDAQ: PULM), a clinical stage biopharmaceutical company developing innovative inhaled therapies to address serious pulmonary and non-pulmonary disease using its patented iSPERSE technology, reported its first quarter 2021 financial results and provides a business update (Press release, Pulmatrix, MAY 11, 2021, View Source [SID1234579674]).

Q1 and Recent Highlights:

PUR1800

Pulmatrix regained full rights to its narrow spectrum kinase inhibitor (NSKI) portfolio, including PUR1800, following Johnsons & Johnson’s Enterprise Innovation’s (JJEI) decision to terminate the Company’s license, development and commercialization agreement. JJEI’s termination of the agreement had no material impact on our financial projections.
Pulmatrix intends to continue the development of PUR1800, with ongoing clinical and toxicology studies to support programs in acute exacerbations in COPD (AECOPD) and other chronic airway diseases.
Initiated the Phase 1b clinical study of PUR1800, dosing 5 of 15 patients to date. Study endpoints include safety, tolerability and exploratory biomarkers to demonstrate target engagement and anti-inflammatory effect. Ph1b top-line data is expected in Q4 2021, shortly after data from 6 and 9-month toxicology studies.
With existing 28-day toxicology results, the Company expects that completion of the PUR1800 Phase 1b will enable a Ph2 efficacy trial in AECOPD. The results from 6 and 9-month toxicology studies underway may expand the PUR1800 opportunity to additional indications which require chronic dosing.
PUR3100

PUR3100 development candidate, a dry powder iSPERSE formulation of dihydroergotamine (DHE) for pulmonary delivery in acute migraine.
Completed dog PK study of PUR3100, demonstrated similar exposure kinetics to modelled kinetics from published data with MAP0004, the MAP Pharmaceuticals pMDI inhaled formulation of DHE.
Pulmazole

Successfully completed a Type C Meeting with the U.S. FDA for the further clinical development of Pulmazole.
On May 10, 2021, we sent a letter to Cipla Technologies LLC ("Cipla") notifying Cipla that it is in material breach of our Development and Commercialization Agreement (the "Cipla Agreement"), dated April 15, 2019, due to Cipla’s anticipatory breach of its obligation under the Cipla Agreement to fund 50% of the development costs for Pulmazole. We have given Cipla 30 days from the date of the letter to reaffirm that it will perform the Agreement in accordance with its terms or we will exercise our contractual right to terminate the agreement for Cipla’s material breach and reacquire all rights to Pulmazole for 25% of its fair market value. In either outcome, Pulmatrix intends to advance Pulmazole clinically to Ph2b.
Hosted KOL investor event featuring presentations by Stewart J. Tepper, M.D., F.A.H.S, Geisel School of Medicine at Dartmouth and Stephen Silberstein, M.D., F.A.C.P., Thomas Jefferson University, detailing the current landscape and unmet need for acute migraine, the potential of novel DHE therapies, and the development plan and preclinical data for PUR3100
Progressing IND-enabling studies with Phase 1/Phase 2 clinical study anticipated to begin Q1 2022.
Corporate:

Completed a registered direct offering with gross proceeds of $40 million extending the Company’s cash runway to fully fund data readouts across its development pipeline including PUR1800 Phase 1b and PUR3100 Phase 1 / Phase 2 studies.
"The first quarter of 2021 has marked a number of significant milestones for Pulmatrix," said Ted Raad, Chief Executive Officer of Pulmatrix. "Each of our iSPERSE enabled programs, ranging from asthma, COPD, and migraine, represents an opportunity to address significant unmet needs of large patient populations. We are pleased to now have the kinase inhibitor portfolio back in our proprietary pipeline following the termination of the development and licensing agreement with Johnson & Johnson. We also remain steadfast in our objective to bring Pulmazole to market and address significant unmet need of patients suffering from ABPA. Our recent notice to Cipla Technologies demonstrates that commitment. With our strong balance sheet, we believe that we can fund operations through planned data milestones for PUR1800 and PUR3100 and, if we ultimately re-acquire Pulmazole from Cipla, begin our Ph2b study."

Financials

As of March 31, 2021, Pulmatrix had $63.4 million in cash and cash equivalents, compared to $31.7 million for the year ended December 31, 2020.

Revenue for the first quarter of 2021 was $1.4 million, compared to $2.8 million for the same period in 2020. The revenue for the first quarter of 2021 and 2020 was the result of the collaboration and licensing agreements with Cipla and JJEI.

Research and development expense was $3.9 million in the first quarter of 2021 compared to $5.3 million for the same period in 2020. The decrease year–over-year was primarily attributable to decreased costs associated with the PUR1800 program and clinical study costs incurred for the Phase 2 Pulmazole study partially offset by preclinical and manufacturing costs for the PUR3100 program.

General and administrative expense was $1.6 million for the first quarter of 2021 compared to $2.2 million for the same period in 2020. The decrease year–over-year was primarily attributable to decreased employment, patent, and consulting costs.

Net loss was $4.1 million for the first quarter of 2021 compared to a net loss of $4.7 million for the same period of 2020.

Olema Oncology Reports First Quarter 2021 Financial Results and Provides Corporate Update

On May 11, 2021 Olema Pharmaceuticals, Inc. ("Olema" or "Olema Oncology," Nasdaq: OLMA), a clinical-stage biopharmaceutical company focused on the discovery, development and commercialization of targeted therapies for women’s cancers, reported an update on recent company developments and reported first quarter financial results for the period ended March 31, 2021 (Press release, Olema Oncology, MAY 11, 2021, View Source [SID1234579673]).

"The first quarter of 2021 was very productive for Olema as we continued to advance our wholly-owned lead candidate, OP-1250, a complete estrogen receptor (ER) antagonist (CERAN), through dose escalation in the ongoing Phase 1/2 clinical trial in ER+ / HER2- breast cancer, and made substantial progress in building our organization," said Sean P. Bohen, M.D., Ph.D., President and Chief Executive Officer of Olema Oncology. "Looking ahead, we remain on track to share initial clinical data at a medical meeting later this year and advance OP-1250 into Phase 2 monotherapy expansion. We also plan to initiate a Phase 1b study to evaluate OP-1250 in combination with a CDK4/6 inhibitor in the second half of 2021. We are in a strong financial position to execute on our strategy and are committed to working toward advancing the standard of care for people living with breast cancer."

Recent Corporate Highlights

Presented nonclinical data on OP-1250 in a late-breaking poster session at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting, held virtually from April 10-15, 2021. Data presented showed that 10 mg/kg OP-1250, a complete estrogen receptor (ER) antagonist (CERAN), was superior to tamoxifen, fulvestrant and ovariectomy in shrinking mutant ESR1-Y537S tumors in an intracranial model of ER+ breast cancer brain metastasis.
Appointed Yi Larson to Olema’s Board of Directors in April 2021. Ms. Larson currently serves as Chief Financial Officer at LianBio and brings significant biotech operational leadership and global healthcare banking expertise.
Strengthened Olema’s research and discovery capabilities with the opening of new laboratory facilities in San Francisco, CA.
Financial Highlights

Cash, cash equivalents and marketable securities as of March 31, 2021 were $327.0 million. Olema anticipates that this balance of cash will be sufficient to fund operations through the end of 2023.
Net loss for the quarter ended March 31, 2021 was $15.3 million, compared to $1.7 million for the same period of the prior year.
Research and development (R&D) expenses were $10.7 million for the quarter ended March 31, 2021, compared to $0.8 million for the same period of the prior year. The increase in R&D expenses was primarily related to the increase in nonclinical development activities, execution of the ongoing Phase 1/2 clinical trial of OP-1250 and higher non-cash stock-based compensation expenses.
General and administrative (G&A) expenses were $4.8 million for the quarter ended March 31, 2021, compared to $0.2 million for the same period of the prior year. The increase in G&A expenses was primarily related to an increase in personnel, public company-related expenses, other corporate costs and higher non-cash stock-based compensation expenses.

Aileron Therapeutics Reports First Quarter 2021 Financial Results and Provides Business Update

On May 11, 2021 Aileron Therapeutics (NASDAQ:ALRN), a chemoprotection oncology company focused on fundamentally transforming the experience of chemotherapy for cancer patients, reported business highlights and financial results for the first quarter ended March 31, 2021 (Press release, Aileron Therapeutics, MAY 11, 2021, View Source [SID1234579672]).

"We continue to work diligently to initiate our first randomized, double-blind, placebo-controlled clinical trial of ALRN-6924 as a novel therapeutic to protect non-small cell lung cancer (NSCLC) patients receiving first-line chemotherapy against various chemotherapy-induced toxicities. Approximately 50% of NSCLC patients have a p53 mutation, suggesting the broad potential impact of ALRN-6924 in this indication alone," said Manuel Aivado, M.D., Ph.D., President and Chief Executive Officer.

Dr. Aivado further commented, "Simultaneously, we are actively planning for the rapid advancement of ALRN-6924 into late-stage development for patients with p53-mutated NSCLC pending the outcome of the Phase 1b trial. Bolstered by our successful capital raises in the first quarter of 2021, we are making near-term strategic investments in CMC, p53 companion diagnostic development, and team scale-up which we expect will not only enable the future advancement of our NSCLC clinical program, but also will provide foundational support for future clinical programs of ALRN-6924 across multiple p53-mutated cancer indications."

Aileron is developing ALRN-6924 to selectively protect healthy cells in patients with cancers that harbor p53 mutations, which are present in over half of all cancer patients, to reduce or eliminate chemotherapy-induced side effects while not interfering with chemotherapy’s attack on cancer cells. This novel concept is known as chemoprotection. By reducing or eliminating multiple chemotherapy-induced side effects, ALRN-6924 may improve patients’ quality of life and help them better tolerate chemotherapy. Enhanced tolerability may result in fewer dose reductions or delays of chemotherapy and the potential for improved efficacy as a result. Given Aileron’s p53 biomarker approach, designed to ensure selective chemoprotection only in healthy cells, coupled with the high prevalence of p53-mutated cancers, the company’s strategy is to ultimately pursue a tumor-agnostic label for ALRN-6924 as a chemoprotective agent in p53-mutated cancers.

First Quarter 2021 Highlights and Recent Updates

Aileron to host upcoming KOL Fireside Chat, "Protecting Cancer Patients from Chemotherapy-Induced Toxicities – A New Paradigm". Moderated by Soumit Roy, Ph.D., Vice President, Healthcare Analyst with JonesTrading Institutional Services LLC, the event will include a discussion on the unmet need and potential for chemoprotection with Alan List, M.D. and Lodovico Balducci, M.D. Dr. List, who recently was appointed Chief Medical Officer of Precision Biosciences, is a renowned hematologist with extensive academic and clinical experience in the research and development of hematology and oncology products. Dr. List is also a member of Aileron’s Scientific Advisory Board. Dr. Balducci, a prominent geriatric oncologist, previously served as Senior Member of the Senior Adult Oncology Program and Medical Director of Affiliates and Referring Physician Relations at the Moffitt Cancer Center. Link here to register for the event, which will take place on Wednesday, May 26, 2021.
Abstract co-authored by Aileron and Foundation Medicine, Inc. to be presented at 2021 ASCO (Free ASCO Whitepaper) Annual Meeting. The abstract, titled, "Gene Sequencing of Serial Tumor Biopsies from a Large Cohort of Cancer Patients Shows Longitudinal Changes in TP53 Mutation Status Are Uncommon" (Abstract #3124), was accepted as a poster presentation at the meeting. Additional details will be announced upon ASCO (Free ASCO Whitepaper)’s online publication of this year’s abstracts later this month.
Announced enrollment expansion for upcoming Phase 1b clinical trial of ALRN-6924 in patients with advanced NSCLC. In February 2021, Aileron announced a 50% expansion of its enrollment target for its upcoming Phase 1b clinical trial of ALRN-6924 in patients with NSCLC undergoing chemotherapy. Aileron plans to enroll 60 patients with advanced p53-mutated NSCLC undergoing treatment with first-line carboplatin plus pemetrexed (with or without immune checkpoint inhibitors). Aileron anticipates this enrollment expansion will enable a more robust exploration of ALRN-6924 as a novel chemoprotective agent to prevent chemotherapy-induced toxicities in the NSCLC patient population and better position the company to rapidly advance ALRN-6924 into late-stage clinical development for NSCLC following the Phase 1b trial.

In the Phase 1b NSCLC trial, patients will be randomized 1:1 to receive either carboplatin/pemetrexed plus 0.3 mg/kg ALRN-6924 or carboplatin/pemetrexed plus placebo for at least four 21-day treatment cycles. Evaluations will include the proportion of treatment cycles free of severe hematological and other toxicities, transfusions and the use of growth factors, as well as the impact on quality of life. Aileron plans to initiate the NSCLC trial in the second quarter of 2021 and anticipates reporting early interim data at the end of 2021 and topline results in mid-2022.
During the first quarter, Aileron completed its Phase 1b evaluation of ALRN-6924 at the recommended phase 2 dose of 0.3 mg/kg in patients with SCLC receiving ALRN-6924 24-hours prior to topotecan and conducted preliminary evaluation of data from additional cohorts. These preliminary findings from 11 additional patients (n=7 patients receiving 0.3 mg/kg ALRN-6924 six hours before topotecan and n=4 patients receiving 0.2 mg/kg ALRN-6924 twenty-four hours before topotecan) were in line with data presented last October and with Aileron’s expectation that administering ALRN-6924 at 0.3mg/kg and 24 hours before topotecan remains the optimal dose and schedule in this patient population. Aileron expects to present results of the Phase 1b SCLC trial at a scientific conference in the second half of 2021.

Raised $55.7 million in aggregate proceeds from the sale of common stock during first quarter 2021, which based on Aileron’s current operating plan, is expected to provide funding into the second half of 2023 and approximately 12 months beyond the anticipated topline results from the NSCLC trial. In January 2021, Aileron completed a registered direct offering of common stock, for a purchase price of $1.10 per share, raising $33.1 million in aggregate net proceeds, after deducting placement agent fees and other offering expenses payable by Aileron. New fundamental and institutional investors, including Acorn Bioventures, BVF Partners, L.P., Maven Investment Partners and Grand Oaks Capital, participated in the offering, in addition to several existing Aileron investors, including Satter Medical Technology Partners and Lincoln Park Capital Fund, LLC. In addition to the registered direct offering, since January 1, 2021, Aileron sold an aggregate of 13,775,399 shares of its common stock for an average purchase price of $1.64 per share, for aggregate net proceeds of $22.6 million, after deducting fees and offering expenses, in "at the market" offerings and under its structured equity line with Lincoln Park Capital Fund, LLC.
Continuing healthy volunteer study to support long-term clinical development strategy for ALRN-6924. The ongoing study, initiated in November 2020, is designed to characterize the time to onset, magnitude, and duration of cell cycle arrest in human bone marrow relative to ALRN-6924 administration. Another goal of the study is to develop a universal dosing regimen for ALRN-6924 for use as a chemoprotection agent across a range of chemotherapies and p53-mutated tumor indications. Aileron expects to present results from the healthy volunteer study at a scientific conference in the second half of 2021.
First Quarter 2021 Financial Results

Cash Position: Cash, cash equivalents and investments at March 31, 2021 were $63.4 million, compared to $13.8 million at December 31, 2020. The company expects, based on its current operating plan, that its existing cash, cash equivalents and investments will fund operations into the second half of 2023.

Research and Development (R&D) Expenses: R&D expenses for the quarter ended March 31, 2021 were $4.3 million, compared to $4.1 million for the corresponding quarter in 2020. The increase of $0.2 million is primarily a result of increased spending on clinical development of ALRN-6924 in connection with the preparation for the upcoming Phase 1b clinical trial in patients with advanced NSCLC patients being treated with first-line chemotherapy of carboplatin and pemetrexed and is partially offset by the effect of cost savings measures implemented in 2020 resulting in decreased spending on employee, facility and other development expenses.

General and Administrative (G&A) Expenses: G&A expenses for the quarter ended March 31, 2021 were $2.7 million, compared to $2.8 million for the corresponding quarter in 2020. The decrease in general and administrative expense is the result of lower headcount and facility costs during the three months ended March 31, 2021 as a result of cost savings measures as compared to the three months ended March 31, 2020 and is partially offset by increased spending on professional services.

Net Loss: Net loss for the quarter ended March 31, 2021 was $7.0 million, compared to $6.7 million for the corresponding quarter in 2020. The basic and diluted net loss per share for the first quarter of 2021 was $0.08 compared to $0.24 for the first quarter of 2020. The change in basic and diluted net loss per share is primarily a result of increased shares outstanding in connection with sales of common stock during the first quarter of 2021.