On November 9, 2021 Mirati Therapeutics, Inc. (Nasdaq: MRTX) a clinical-stage oncology company, reported that it intends to offer and sell in an underwritten public offering $500 million of shares of its common stock (Press release, Mirati, NOV 9, 2021, View Source [SID1234594908]). In addition, Mirati expects to grant the underwriters of the offering a 30-day option to purchase up to an additional 15% of the total shares offered in the public offering 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.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

Goldman Sachs & Co. LLC, SVB Leerink LLC and Cowen and Company, LLC are acting as joint book-running managers 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, NY 10282, or by telephone at (866) 471-2526, or by email at [email protected]; or from SVB Leerink LLC, Attention: Syndicate Department, 53 State Street, 40th Floor, Boston, MA 02109, by telephone at (800) 808-7525, ext. 6105, or by email at [email protected]; or from Cowen and Company, LLC, c/o Broadridge Financial Solutions, Attention: Prospectus Department, 1155 Long Island Avenue, Edgewood, NY 11717, or by telephone at (833) 297-2926, 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 November 9, 2021 I-Mab (Nasdaq: IMAB), a clinical-stage biopharmaceutical company committed to the discovery, development, and commercialization of novel biologics, and ABL Bio, Inc. (Kosdaq:298380, hereafter "ABL"), a clinical-stage biotech developing bispecific antibody technology for immune-oncology and neurodegenerative diseases, reported preclinical data of their 4-1BB bispecific antibodies at the 2021 Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) Annual Meeting (Press release, I-Mab Biopharma, NOV 9, 2021, View Source [SID1234594924]). The new data demonstrate the unique mechanisms of action of TJ-CD4B/ABL111 and TJ-L14B/ABL503 which have resulted in localized drug action and reduced systemic toxicity, as well as sustained anti-tumor efficacy.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

Stimulation of 4-1BB is a promising therapeutic strategy for improving the current immunotherapy for multiple cancers. TJ-CD4B/ABL111 and TJ-L14B/ABL503, both jointly developed by I-Mab and ABL, are undergoing phase 1 clinical studies in the United States.

"Bispecific antibodies are rapidly recognized for their transformative potential, and our pipeline of highly-differentiated 4-1BB bispecific therapies are key components of our biologics pipeline development strategy," said Dr. Taylor Guo, Chief Scientific Officer of I-Mab. "Dose-limiting toxicities have hampered clinical development of 4-1BB targeting molecules as a drug class. The studies being presented at SITC (Free SITC Whitepaper) suggested that both our bispecific assets could have the ability to overcome this common problem, and we are confident that this differentiation places TJ-CD4B/ABL111 and TJ-L14B/ABL503 at the forefront of 4-1BB bispecific development."

"The preclinical data from this pair of bispecific molecules prove that our ‘Grabody-T’ platform effectively reduces peripheral toxicity by allowing the activation of T cells only in the tumor microenvironment," said Dr. Sang Hoon Lee, CEO of ABL Bio. "We look forward to further validating its therapeutic potential in the ongoing clinical studies and as we continue to develop 4-1BB bispecific antibodies in various cancer indications."

Key data highlights:

TJ-CD4B/ABL111

Poster title (#702): TJ-CD4B (ABL111), a Claudin18.2-targeted 4-1BB tumor engager induces potent tumor-dependent immune response without dose-limiting toxicity in preclinical studies

The preclinical studies confirmed the unique pharmacodynamic data and safety of TJ-CD4B/ABL111 in animal models and cell cultures. Analysis of the data found:

Potent, anti-tumor activity was observed with the proliferation of immune cells in the tumor microenvironment (TME) as well as an increase in memory T cells in the peripheral blood, suggesting long-term immunity against the tumor.
TJ-CD4B/ABL111 was well tolerated in non-human primates and did not induce a systemic immune response or liver toxicity up to levels of 100mg/kg.
Activation of immune pathways by TJ-CD4B/ABL111 was demonstrated by a pro-inflammatory profile and increased gamma interferon-regulated gene expression in primary human CD8+ T cells co-cultured with CLDN18.2 expressing cells.
TJ-L14B/ABL503

Poster title (#892): ABL503 (TJ-L14B), PD-L1x4-1BB bispecific antibody induces superior anti-tumor activity by PD-L1-dependent 4-1BB activation with the increase of 4-1BB+CD8+ T cells in tumor microenvironment

The preclinical study data confirms the unique mechanism of action of TJ-L14B/ABL503 and its potential to treat resistance to PD-L1 therapies. Analysis of the data found:

PD-L1-dependent stimulation of the 4-1BB signaling pathway was demonstrated in 4-1BB bioassays with PD-L1 expressing tumor cells
More potent 4-1BB activation by TJ-L14B/ABL503 was observed at higher PD-L1 expression confirming the requirement of PD-L1 on both tumor and immune cells for optimal activity. Cytokine release assays have also demonstrated minimal peripheral toxicity with TJ-L14B/ABL503
The in vivo efficacy of TJ-L14B/ABL503 was demonstrated in animal models with tumors expressing different levels of PD-L1. TJ-L14B/ABL503 showed anti-tumor efficacy across the PD-L1 levels. In particular, TJ-L14B/ABL503 demonstrated superior anti-tumor efficacy than atezolizumab in tumors with low PD-L1 expression
In vitro tumor-killing activity of TJ-L14B/ABL503 was superior compared to atezolizumab when tested in organoid system, even in organoids from atezolizumab non-responders
Pharmacodynamic changes in TILs and blood were evaluated in animal models. An increase in 4-1BB+ cells, CD8+ T cells, and effector memory T cells was observed in the TME and blood, indicating a strong and long-lasting anti-tumor immune response
Treatment with TJ-L14B/ABL503 increased MIG/CXCL9, MIP-1b/CCL4, and s4-1BB in the serum, and can potentially be used as pharmacodynamic markers in clinical trials
About TJ-CD4B/ABL111

TJ-CD4B, also known as ABL111, is a Claudin 18.2 and 4-1BB bispecific antibody capable of binding to tumor cells expressing Claudin 18.2, i.e., gastric cancer and pancreatic cancer cells, and stimulating intra-tumoral T cells by the 4-1BB arm designed to be activated only upon tumor engagement while silent elsewhere. TJ-CD4B/ABL111 effectively maintains a strong tumor binding property and anti-tumor activity attributable to a synergistic effect of both Claudin 18.2 antibody and 4-1BB antibody while it avoids or minimizes liver toxicity and systemic immunotoxicity commonly seen with 4-1BB antibodies as a drug class. Being developed under collaboration between I-Mab and ABL, TJ-CD4B/ABL111 is currently being investigated in a phase 1 clinical study in the U.S.

About TJ-L14B/ABL503

Being developed jointly with ABL, TJ-L14B/ABL503 is a differentiated PD-L1-based bispecific antibody with the PD-L1 arm as the tumor-dependent T-cell activator and the 4-1BB arm as the conditional T cell activator upon tumor engagement. Using ABL’s "Grabody-T" bispecific antibody platform technology, TJ-L14B/ABL503 stimulates 4-1BB activation only in the presence of PD-L1 expressing tumor cells to minimize the risk of off-tumor toxicity. Preclinical studies have demonstrated that the bispecific antibody shows better anti-tumor activity than equimolar doses of single agents alone or in combination. Phase 1 study in currently being conducted in the U.S.

On November 9, 2021 Carevive Systems ("Carevive") the leading oncology-focused health technology company centered on understanding and improving the experience of patients with cancer, reported that it has entered into a clinical research collaboration with NorthShore University HealthSystem (NorthShore) to utilize Carevive’s Patient Reported Outcomes Mobile Platform (PROmpt) system in the collection of critical patient data (Press release, Carevive Systems, NOV 9, 2021, View Source [SID1234594940]). Part of Carevive OPT-IN, a consortium of clinician investigators utilizing PROmpt, the NorthShore partnership will capture real-world patient data that will help improve the overall patient experience during treatment. PROmpt will summarize clinical, anecdotal, and demographic information associated with patient treatment, in an effort to positively improve patient outcomes.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"The patient information accumulated during our collaboration with NorthShore will enable the PROmpt system to collect patient data in real-time that is critical to understanding both medical and quality of life needs of cancer patients, and learn where care improvements are necessary," said Debra Wujcik, PhD, RN, FAAN, VP, Research and Clinical Operations with Carevive. "Our PROmpt platform offers a highly efficient and fully-integrated data capture system that allows our clinical partners at NorthShore to gather knowledge about the entire patient experience and use that information to make the necessary care and treatment modifications. It is our hope that the patient registries developed during these studies will enable us to impact future patient care within other clinical settings."

The PROmpt patient self-assessment platform system, allows cancer patients the ability to receive important information once they report they are experiencing a new symptom. This information will help guide each patient on their care journey and on what steps to take next with their clinical care team. Using the PROmpt system, clinicians now have the tools to care and monitor patients remotely using the system’s platform. The data capture consists of a simple-to-use process that includes a direct patient registration, initial and weekly surveys, automated program response, and clinical notification. Each data set retrieved through this process will be used by NorthShore’s clinicians to not only improve overall patient care, but to also tailor modifications that are unique to each patient and address those impediments to treatment success.

"Carevive’s integrated patient platform holds great promise in capturing and understanding the data that is essential for the development of successful cancer treatment programs by our clinical teams," stated Nicklas Pfanzelter, M.D. and Oncologist, NorthShore University HealthSystem. "Our alliance with Carevive underscores NorthShore’s commitment to those cancer patients receiving treatment within our hospital network and, also those newly-diagnosed who may present themselves in the future. We look forward to partnering with Carevive and the application of our integrated clinical and technical capabilities to help improve cancer treatment."

Anyone interested in learning more about Carevive OPT-IN or benefits of the PROmpt system, can visit the Carevive website.

On November 9, 2021 Kronos Bio, Inc. (Nasdaq: KRON), a company dedicated to transforming the lives of those affected by cancer, reported recent business progress and third-quarter financial results (Press release, Kronos Bio, NOV 9, 2021, View Source [SID1234594992]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"As we approach the end of the year, we look forward to reporting interim data from the ongoing Phase 1/2 study of our internally discovered CDK9 inhibitor, KB-0742, capping off a year of significant progress," said Norbert Bischofberger, Ph.D., president and chief executive officer of Kronos Bio. "In addition to continued execution across our clinical stage programs, I am also pleased with the progress we are making with our pipeline – particularly the addition of two new discovery programs, which underscore the capabilities of our product engine."

Pipeline Progress
Kronos Bio reported it has initiated two new discovery programs, each focused on a distinct target or node identified through the company’s research and mapping of the MYC and AR transcriptional regulatory networks (TRNs).

Target 1: MYC TRN. Dysregulation of the MYC TRN is a hallmark of cancer and occurs in a large percentage of cancers. The company’s existing development candidate, KB-0742, targets CDK9 and is being evaluated in a Phase 1/2 clinical study. KB-0742 is intended to target MYC dysregulation in the context of MYC genomic amplification, which occurs in 30% of all solid tumors. The new Target 1 program is aimed at modulating a protein-protein interaction in the MYC TRN with the objective of treating additional MYC-dysregulated cancers beyond those targeted by KB-0742.
Target 2: AR TRN. Dysregulation of the AR (androgen receptor) TRN is a primary driver of prostate cancer. Although therapies that directly inhibit the androgen receptor already exist, many patients with prostate cancer ultimately develop resistance to these therapies and patients with castration-resistant prostate cancer (CRPC) have a particularly poor prognosis. This new program aims to overcome resistance to current therapies by targeting an AR cofactor that selectively modulates the AR TRN in the context of CRPC.
The company anticipates identifying a lead candidate and submitting an Investigational New Drug (IND) application out of one of its discovery programs in 2023.
Additionally, Kronos Bio yesterday announced a multi-year collaboration with Tempus, a leader in artificial intelligence and precision medicine. The agreement will provide Kronos Bio with access to real-world patient genomic and transcriptomic data and data analytics tools, with the goal of accelerating the development of the company’s current and future clinical portfolio.

Third-Quarter Company Highlights

Kronos Bio presented preclinical data characterizing the pharmacokinetic (PK) and pharmacodynamic (PD) profile of KB-0742 in a poster at the AACR (Free AACR Whitepaper)-NCI-EORTC Virtual AACR-NCI-EORTC (Free AACR-NCI-EORTC Whitepaper) International Conference on Molecular Targets and Cancer Therapeutics (EORTC-NCI-AACR) (Free ASGCT Whitepaper) (Free EORTC-NCI-AACR Whitepaper) in October 2021. These data build on results first shared at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) meeting earlier this year. The new data demonstrated a favorable preclinical PK profile and human PK projection that support the intermittent dosing schedule for patients in the Phase 1/2 study.
The U.S. Food and Drug Administration cleared the company’s IND for lanraplenib, a next-generation spleen tyrosine kinase (SYK) inhibitor. This allows Kronos Bio to proceed with its planned Phase 1b/2 clinical trial of the compound in patients with relapsed or refractory FLT3-mutated acute myeloid leukemia (AML) in combination with gilteritinib.
Upcoming Milestones

The company plans to report interim safety, PK and PD data in Q4 2021 from the ongoing dose escalation phase of its Phase 1/2 clinical trial of KB-0742, which is being developed to treat MYC-amplified or over-expressing solid tumors.
Kronos Bio remains on track to dose the first patient in its planned Phase 3 clinical trial of entospletinib before the end of the year, with a data readout expected in the second half of 2023. This trial will assess measurable residual disease (MRD) negative complete response as the primary endpoint to support potential accelerated approval in patients newly diagnosed with NPM1-mutated AML and eligible for intensive induction chemotherapy.
The company expects to dose the first patient in the first of two planned Phase 1b/2 clinical trials of lanraplenib in the first quarter of 2022. This first trial will evaluate lanraplenib in patients with relapsed or refractory FLT3-mutated AML.
Kronos Bio plans to initiate a second Phase 1b/2 clinical trial of lanraplenib, in combination with venetoclax/azacitidine in patients newly diagnosed with NPM1-mutated and/or FLT3-mutated AML who are older than age 75 or not eligible for intensive induction chemotherapy in the first half of 2022.
Third Quarter Financial Highlights

Cash, Cash Equivalents and Investments: As of September 30, 2021, cash, cash equivalents and investments totaled $398.4 million.

R&D Expenses: Research and development expenses were $24.7 million for the third quarter of 2021, which includes non-cash stock-based compensation expense of $3.5 million.

G&A Expenses: General and administrative expenses were $9.0 million for the third quarter of 2021, which includes non-cash stock-based compensation expense of $3.6 million.

Net Loss: Net loss for the third quarter of 2021 was $33.6 million, or $0.61 per share, including non-cash stock-based compensation expense of $7.1 million.

On November 9, 2021 AnPac Bio-Medical Science Co., Ltd. (NASDAQ: ANPC, the "Company"), a biotechnology company with operations in China and the United States focusing on early cancer screening and detection, reported the pricing of an underwritten public offering of 1,301,928 of its American Depositary Shares ("ADSs") at a public offering price of $2.22 per share, for gross proceeds to the Company of approximately $2.9 million, before deducting the underwriting discount and other offering expenses payable by the Company (Press release, Anpac Bio, NOV 9, 2021, View Source [SID1234595377]). This includes the full exercise of the underwriter’s over-allotment option.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

EF Hutton, division of Benchmark Investments, LLC is acting as the sole book-running manager for the offering. The offering is expected to close on or about November 12, 2021, subject to customary closing conditions.

The shares of ADSs described above are being offered by AnPac Bio-Medical Science Co., Ltd. pursuant to a "shelf" registration statement on Form F-3 (File No. 333-256630) that became effective with the Securities and Exchange Commission (SEC) on June 7, 2021, the base prospectus contained therein and the accompanying prospectus supplement.

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