On December 22, 2021 Adagene Inc. ("Adagene") (Nasdaq: ADAG), a biopharmaceutical company committed to transforming the discovery and development of novel antibody-based immunotherapies, reported achievement of a key milestone in its ongoing collaboration with Exelixis for development of novel masked antibody-drug conjugate (ADC) candidates leveraging Adagene’s proprietary SAFEbody precision masking technology (Press release, Adagene, DEC 22, 2021, View Source [SID1234597597]). Under the terms of a collaboration and licensing agreement established in early 2021, Adagene will receive a $3 million milestone payment for successful nomination of lead SAFEbody candidates for one of its collaboration programs.

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"We are extremely proud of successfully providing lead SAFEbody candidates to Exelixis following the start of our collaboration earlier this year. Exelixis’ selection of these lead candidates further validates our proprietary SAFEbody technology and highlights the prowess of our overall DPL platform," said Peter Luo, Ph.D., Co-founder, Chief Executive Officer, and Chairman of Adagene. "Our SAFEbody masking technology is receiving clinical validation in our ongoing clinical trial from our anti-CTLA-4 monoclonal antibody program, and also marks a potential paradigm shift in the way a highly potent modality such as ADCs can be designed and developed, ultimately helping to improve the lives of patients suffering from cancer and other debilitating diseases."

Under the terms of the agreement, Adagene received an upfront payment of $11 million and Exelixis can nominate two targets for development of SAFEbody candidates during the collaboration. Adagene is eligible for development and commercialization milestones, as well as royalties on net sales of products developed around each of these targets.

SAFEbody technology is designed to overcome safety and tolerability challenges associated with many antibody therapeutics by using precision masking technology to shield the binding domain of the biologic therapy. This allows for improved tumor-specific targeting of antibodies, while minimizing on-target off-tumor toxicity in healthy tissues, a longstanding challenge with many antibody therapeutics.

In addition to ongoing collaborations, Adagene also applies its SAFEbody technology to develop candidates for its wholly-owned deep, broad and differentiated pipeline. These include ADG126, an anti-CTLA-4 SAFEbody in phase 1 dose escalation as monotherapy, as well as five highly differentiated programs in IND-enabling studies such as ADG153, an anti-CD47 SAFEbody using the potent IgG1 isotype, and ADG152, anti-CD20xCD3 bispecific POWERbody T-cell engager. A total of five antibodies are in clinical development by Adagene and its partners, leveraging the company’s AI-driven antibody discovery and development platform.

On December 22, 2021 Agios Pharmaceuticals, Inc. (NASDAQ: AGIO), a leader in the field of cellular metabolism to treat genetically defined diseases, reported that the company is scheduled to present at the virtual 40th Annual J.P. Morgan Healthcare Conference on Wednesday, January 12, 2022, at 7:30 a.m. ET (Press release, Agios Pharmaceuticals, DEC 22, 2021, View Source [SID1234597598]).

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A live webcast of the presentation can be accessed under "Events & Presentations" in the Investors section of the company’s website at www.agios.com. A replay of the webcast will be archived on the Agios website for at least two weeks following the presentation.

On December 22, 2021 The Life Raft Group reported that highlighted recent clinical trials that are still recruiting in the U.S. which investigate potential treatments for GIST patients (Press release, The Life Raft Group, DEC 22, 2021, View Source [SID1234597850]).

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Our database, gisttrials.org, lists over 70 trials that are GIST-related which are ongoing around the world. Currently there are 11 GIST-related trials recruiting in the United States. (Of these 11, two are no Phase (0), three are Phase 1, five are Phase 2, one is Phase 1/2.) This article gives a sampling of four trials currently recruiting for KIT/PDGFRa mutant GIST, SDH-deficient GIST (2), and a no Phase Surgery trial for all GIST Types. For further information about GIST trials including international trials, visit: The Life Raft Group Clinical Trials Website.

About Phase 1 trials
It is important to recognize that Phase I studies are held to find the highest dose of the new treatment that can be given safely without causing severe side effects.

• The first few people in the study get a very low dose of the treatment and are watched very closely. If there are only minor side effects, the next few participants get a higher dose. This process continues until doctors find a dose that’s most likely to be and effective treatment while having an acceptable level of side effects.

• Safety is the main concern. The research team monitors participants and watches for severe side effects. Due to the small numbers of people in Phase I studies, rare side effects may not be seen until later phases of the trial when more people are receiving the treatment.

• While some people may benefit from being on one, disease response is not the main purpose of a Phase I trial. Phase I trials carry the most potential risk, but these studies do help some patients. For those with life-threatening illnesses, weighing the potential risks and benefits carefully is key. Sometimes people choose
to join Phase I trials when all other treatment options have already been tried.

Phase I trials carry the most potential risk, but these studies do help some patients. For those with life-threatening illnesses, weighing the potential risks and benefits carefully is key. Sometimes people choose
to join Phase I trials when all other treatment options have already been tried.

For patients with advanced KIT/PDGFRa mutant GIST:

NB003 Phase 1 – "A Study of NB003 in Patients With Advanced Malignancies"
Site is Memorial Sloan Kettering Cancer Center NY, NY.
Principal Investigator: Dr. Ping Chi. The trial started 8/6/2021. Dose escalation phase will be followed by
an expansion phase. Plans are to recruit 36 over a period of 20 months. NB003 oral tablets are administered twice daily for repeated 28-day cycles.

Primary objectives are incidence of dose limiting toxicity and incidence of adverse events. Tumor sample collection is required. Includes GIST and other solid tumors with either KIT or PDGFRa mutations. Includes patients with advanced GIST who have progressed on or had an intolerability to imatinib and other standard of care (SoCs) or refused other SoCs.

Sponsor is Ningbo Newbay Technology Development Co., Ltd in China. Obtained development rights from AstraZeneca in 2020. NB003 was previously called AZD3229. AstraZeneca employee authors described AZD3229 translational relevance in a 2019 paper: "AZD3229 has potential as a best-in-class treatment for patients with GIST with mutations in KIT and PDGFRα, and this compound may overcome the limitations experienced with existing treatment options in the clinic which are limited by off-target effects leading to drug holidays and dose reductions leading to lack of optimum efficacy." Contact at MSKCC, 646-888-3915
or email [email protected] NCT04936178

For patients with SDH-deficient GIST

Temozolomide Phase 2 – "Temozolomide (TMZ) In Advanced Succinate Dehydrogenase (SDH) Mutant/Deficient Gastrointestinal Stromal Tumor (GIST)".

Trial sites include University of California San Diego, University of Miami, Oregon Health Science University, Portland, Fox Chase Cancer Center, Philadelphia. Principal Investigators include Adam Burgoyne, Jon Trent, Mike Heinrich, Margaret von Mehren. Started 9/12/2018.

Recruiting 23 participants over 48 months. Temozolomide (Temodar) tablets taken orally once a day for 21 days followed by seven days off drug for each 28-day drug cycle.

Primary objective is overall response rate. Patients will continue treatment until disease progression or unacceptable toxicity. Includes patients who have pathologically confirmed SDH-mutant/deficient GIST and tumors measurable on CT scans.

Information concerning the rationale for use of Temozolomide in SDH-deficient GIST can be found in the following reports:

• 1/7/2019 – "Preferential MGMT methylation could predispose a subset of KIT/PDGFRA-WT GISTs, including SDH-deficient ones, to respond to alkylating agents"

• 10/12/2020 – "Abnormal MGMT Promoter Methylation in Gastrointestinal Stromal Tumors: Genetic Susceptibility and Association with Clinical Outcome"

Information concerning side effects of TMZ in GIST patients can be found in the following report:

• 12/4/2003 – "A two-arm phase II study of temozolomide in patients with advanced gastrointestinal stromal tumors and other soft tissue sarcomas".

Sponsor is Dr. Adam Burgoyne. Contact at UCSD at 858-822-3092 or email [email protected] NCT03556384

Rogaratinib Phase 2 – "Testing the Anti-cancer Drug, Rogaratinib (BAY 1163877), for Treatment of Advanced Sarcoma With Alteration in Fibroblast Growth Factor Receptor (FGFR 1-4), and in Patients With SDH-deficient Gastrointestinal Stromal Tumor (GIST)"

Trial sites include: Dana-Farber Boston, Boston, The National Cancer Institute Bethesda, City of Hope Duarte, CA, Memorial Sloan Kettering New York, NY, Washington University School of Medicine St. Louis, University of Pittsburgh Cancer Institute.

Principal Investigators include: Suzanne George, A. P. Chen, Mark Agulnik, Katherine Thornton, Brian Van Tine, Melissa Burgess. Started 2/1/2021.

Recruiting 48 participants over 24 months. Patients take Rogaratinib pills twice daily on days 1-28. Treatment repeats every 28 days for up to 24 cycles in the absence of disease progression or unacceptable toxicity.

Primary objective is to estimate the objective radiographic response rate. Serial biopsies may be required. Confirmed SDH-deficient patients must have measurable disease on scans. The sponsor is the National Cancer Institute.

The rationale for targeting FGFR in SDH-deficient GIST is provided in the following paper:

• 10/16/2019 – "Altered chromosomal topology drives oncogenic programs in SDH-deficient GISTs"
Information about the safety and side effects of Rogaratenib is provided in the following paper reporting results of a Phase 1 dose escalation study:

• 8/9/2019 – "Rogaratinib in patients with advanced cancers selected by FGFR mRNA expression: a phase 1 dose-escalation and
dose-expansion study."

Contact information is available for each site at clinicaltrials.gov NCT04595747

For all GIST patients:

Surgery, No Phase – "Surgery in Gastrointestinal Stromal Tumors (GISTs)
for Treatment, Tumor Modeling, and Genomic Analysis"

National Institute of Health Clinical Center in Bethesda, MD.

Principal Investigator is Dr. Andrew M Blakely. Started 12/18/2020. Recruiting 400 participants over 20 years. Participants will be monitored every 6-12 months at the NIH Clinical Center, for up to 10 years before having surgery. If they need surgery, it will be performed at the NIH. Then, they will be monitored every 6-12 months, for up to five years after surgery.

If a participant has surgery, tumor tissue samples will be taken. If a participant does not need surgery, their participation will end after 10 years. If they have surgery, the five-year monitoring period will restart after each surgery.

The overall objective is to follow people with GISTs and collect tumor tissue so that it can be studied in the lab. The Primary objective is to evaluate and follow patients with GISTs, particularly WT or treatment-refractory non-WT, to support translational research for this rare disease Time Frame: on-going. People aged six and older who have GIST are eligible.

Inclusion criteria include: Histological confirmation or clinical presentation suspicious of GIST; histological confirmation will be preferably by review of archival tissue if available, fresh biopsy will not be required if inadequate tissue sample.

On December 22, 2021 Ligand Pharmaceuticals Incorporated (NASDAQ: LGND) reported that its partner CStone Pharmaceuticals (HKEX: 2616) reported that it has received approval from China’s National Medical Products Administration (NMPA) for sugemalimab (Cejemly), an OmniAb-derived anti-PD-L1 monoclonal antibody, for the first-line treatment of metastatic (stage IV) non-small cell lung cancer (NSCLC) in combination with chemotherapy (Press release, Ligand, DEC 22, 2021, View Source [SID1234597599]).

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Sugemalimab is an anti-PD-L1 antibody in development to treat various cancers. Positive results from the planned interim analysis of the Phase 3 study in stage IV NSCLC (GEMSTONE 302) were reported in August 2020 and updated data were presented in a late-breaking oral presentation at the IASLC 2021 World Conference on Lung Cancer, showing that sugemalimab plus chemotherapy continued to demonstrate improvement in progression-free survival (PFS) than seen in the interim analysis. CStone reported in May 2021 that the Phase 3 study evaluating sugemalimab in stage III NSCLC (GEMSTONE-301) met its primary endpoint of prolonged PFS in a planned interim analysis. On September 2, CStone announced that the NMPA accepted the NDA of sugemalimab for consolidation therapy in patients with unresectable stage III NSCLC who have not progressed after concurrent or sequential radiotherapy and chemotherapy.

In addition to NSCLC, sugemalimab is being investigated in a Phase 2 registrational study for relapsed or refractory extranodal natural killer/T-cell lymphoma (R/R ENKTL) and in Phase 3 registrational studies for gastric cancer and esophageal cancer. Sugemalimab has received breakthrough therapy designation from both the U.S. Food and Drug Administration and Center for Drug Evaluation (CDE) of China’s NMPA for the treatment of adult patients with R/R ENKTL.

"Today’s NMPA approval is an important milestone for CStone and their robust sugemalimab development program," said John Higgins, CEO of Ligand Pharmaceuticals. "This approval comes just months after the first regulatory approval for an OmniAb-derived medicine and further highlights the transformative year for OmniAb as our partners’ late-stage pipelines continue to advance. We believe OmniAb’s broad use and differentiated technology will drive continued favorable clinical and regulatory events in the coming years."

About sugemalimab

Sugemalimab (Cejemly) is an investigational anti-PD-L1 monoclonal antibody developed by CStone and discovered using the OmniRat transgenic animal platform, which can generate fully human antibodies. As a fully human, full-length anti-PD-L1 monoclonal antibody, Cejemly mirrors the natural G-type immunoglobulin 4 (IgG4) human antibody, which may reduce the risk of immunogenicity and potential toxicities in patients.

In the planned interim analysis of the Phase 3 GEMSTONE 302 study for the first-line treatment of patients with stage IV NSCLC, sugemalimab in combination with chemotherapy met the primary endpoint and significantly prolonged progression-free survival (PFS) and reduced the risk of disease progression or death by 50% [95% CI: 0.39, 0.64], p<0.0001. Updated data of the GEMSTONE-302 study showed that the risk of disease progression or death was reduced by 52%, and an encouraging trend in overall survival (OS) was observed. The investigator-assessed PFS was 9.0 months vs 4.9 months [HR=0.48 (95% CI: 0.39, 0.60, p<0.0001)] and the median OS was 22.8 months vs 17.7 months, HR=0.67, although the OS events had not yet met the pre-defined interim analysis plan. Sugemalimab plus chemotherapy had a well-tolerated safety profile, and no new safety signals were observed.

In the planned interim analysis of the GEMSTONE-301 study in stage III NSCLC, the independent data monitoring committee assessed that it reached the preset primary study endpoint. The results of the trial showed that sugemalimab as a consolidation treatment significantly improved PFS assessed by the blinded independent center review, and the difference was statistically significant and clinically significant. The PFS results assessed by the investigator were consistent with the primary study endpoint. Sugemalimab was well-tolerated with no new safety signals. Subgroup analysis showed that both patients who received concurrent or sequential radiotherapy and chemotherapy before the trial showed clinical benefit. On September 2, 2021, CStone announced that the NMPA accepted the NDA of sugemalimab for stage III NSCLC.

Currently, sugemalimab is being investigated in several ongoing clinical trials, including a Phase 2 registration study for R/R ENKTL and four Phase 3 registrational studies in Stage III NSCLC, Stage IV NSCLC, gastric cancer and esophageal cancer.

About OmniAb

The OmniAb discovery platform provides Ligand’s pharmaceutical industry partners access to the diverse antibody repertoires and high-throughput screening technologies to enable discovery of next-generation therapeutics. At the heart of the OmniAb platform is the Biological Intelligence (BI) of our proprietary transgenic animals, including OmniRat, OmniChicken and OmniMouse that have been genetically modified to generate antibodies with human sequences to facilitate development of human therapeutic candidates. OmniFlic (transgenic rat) and OmniClic (transgenic chicken) address industry needs for bispecific antibody applications though a common light chain approach, and OmniTaur features unique structural attributes of cow antibodies for complex targets. OmniAb animals comprise the most diverse host systems available in the industry and they are optimally leveraged through computational antigen design and immunization methods, paired with high-throughput microfluidic-based single B cell screening and deep computational analysis of next-generation sequencing datasets to identify fully human antibodies with superior performance and developability characteristics. An established core competency focused on ion channels and transporters further differentiates our technology and creates opportunities to further leverage across modalities, including antibody-drug conjugates and others. The OmniAb suite of technologies and differentiating computational capabilities and BI features are combined to offer a highly efficient and customizable end-to-end solution for the growing discovery needs of the global pharmaceutical industry.

On December 22, 2021, Achieve Life Sciences, Inc. ("Achieve") reported that entered into a contingent convertible debt agreement (the "Debt Agreement") with Silicon Valley Bank, in its capacity as administrative agent and lender (in such capacity, "Agent"), Silicon Valley Bank, as a lender ("SVB"), and SVB Innovation Credit Fund VIII, L.P., as a lender (together with SVB, the "Lenders"), pursuant to which the Lenders provided term loans having an aggregate original principal amount of $15.0 million (the "Convertible Term Loan") (Filing, 8-K, OncoGenex Pharmaceuticals, DEC 22, 2021, View Source [SID1234597601]). Subject to the terms and conditions of the Debt Agreement, upon Achieve’s request on or prior to December 31, 2022 and Agent’s and each Lender’s receipt of all necessary internal and credit approvals, Achieve may borrow additional term loans in an aggregate original principal amount of up to $10.0 million. Achieve’s obligations under the Debt Agreement are secured by substantially all of Achieve’s assets, other the intellectual property.

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The Convertible Term Loan matures on December 22, 2023; provided that such date will be extended to December 22, 2024 upon the occurrence of both (i) Achieve’s written request and (ii) Agent’s confirmation that the Agent and Lenders agree to extend the maturity date upon receipt of all necessary internal and credit approvals for such extension. Interest is calculated on the outstanding principal amount of the Convertible Term Loan at the aggregate of (a) a floating rate per annum equal to the greater of (i) 2.25% and (ii) the prime rate minus 1.0%, which interest shall be payable in cash monthly in arrears, and (b) 7.0% per annum, compounded monthly, which shall be payable on the earlier to occur of the maturity date and the date that the Convertible Term Loan is converted in to Achieve’s common stock.

The conversion feature grants the Lenders or, pursuant to an assignment, any designee thereof (each, a "Conversion Right Holder", and collectively, the "Conversion Right Holders") the right to convert part or all of the outstanding principal of the Convertible Term Loan, plus accrued and unpaid interest into shares of Achieve’s common stock at a conversion price equal to $9.34, as may be adjusted for stock splits, stock dividends, reorganizations, recapitalizations and the like (the "Conversion Price"). The conversion rights may be exercised at each Conversion Right Holder’s option any time prior to repayment of the Convertible Term Loan. Additionally, the outstanding principal of the Convertible Term Loan, plus accrued and unpaid interest, will be converted into shares of Achieve’s common stock at the Conversion Price on the date where the closing price per share of Achieve’s common stock is equal to or greater than $24.00 for thirty consecutive trading days prior to such date.

The Convertible Term Loan may be repaid at Achieve’s election by paying the Lenders an amount equal to (i) if such repayment is made on or before the eighteen month anniversary of the closing date, 125% of the outstanding principal balance (including compounded interest), plus accrued and unpaid interest, and (ii) if such repayment is made after the eighteen month anniversary of the closing date, 150% of the outstanding principal balance (including any compounded interest), plus accrued and unpaid interest. Notwithstanding the foregoing, if Achieve elects to repay the Lenders and in the twelve month period following such repayment enters to an agreement, commitment, letter of intent or memorandum of understanding or the like, binding or nonbinding, with any third party respecting an acquisition, and such acquisition is subsequently consummated, if the aggregate gross proceeds that would have been payable to the Conversion Right Holders in connection with such acquisition had Achieve not repaid the Convertible Term Loan and the Conversion Right Holders had exercised, in connection with such acquisition, the right to convert the Convertible Term Loan into shares of Achieve’s common stock, then Achieve shall pay to the Lenders as an additional call price, the difference between such proceeds as would have been payable to the Conversion Right Holders in connection with such acquisition and the payment actually paid to the Lenders.

The Debt Agreement contains customary affirmative and restrictive covenants, including covenants regarding the incurrence of additional indebtedness or liens, investments, transactions with affiliates, delivery of financial statements, payment of taxes, maintenance of insurance, dispositions of property, mergers or acquisitions, among other customary covenants. Achieve is also restricted from paying dividends or making other distributions or payments on its capital stock, subject to limited exceptions. The Debt Agreement also includes customary representations and warranties, events of default and termination provisions. The Lenders may not engage in any short sales of, or other hedging transactions in, Achieve’s common stock while any amounts are outstanding under the Debt Agreement.

In connection with the Debt Agreement, Achieve entered into a Registration Rights Agreement (the "RRA") with the Lenders, pursuant to which Achieve may be required to register for resale shares of its common

stock issued to the Conversion Right Holders upon the conversion of outstanding debt under the Debt Agreement. Achieve’s obligations under the RRA will terminate with respect to a holder of applicable registrable securities upon the earlier to occur of (a) the time when such holder delivers a notice demanding registration or (b) Achieve would be required to give notice to such holder of its intention to file an applicable registration statement, in either case if (x) the aggregate number of registrable securities then issued and issuable to such holder and to such holder’s affiliates, together with all other shares then held beneficially and/or of record by such holder and its affiliates, does not exceed seven percent (7%) of Achieve’s then-total shares issued and outstanding (calculated including all such registrable securities and other shares), or (y) Achieve and such holder mutually reasonably agree that all registrable securities then issued and issuable to such holder and its affiliates may then be sold by such holder without the requirement to be in compliance with Rule 144 promulgated under the Securities Act of 1933, as amended (the "Rule 144") and otherwise without restriction or limitation pursuant to Rule 144.

The foregoing descriptions of the Debt Agreement, the Convertible Term Loans and RRA do not purport to be complete and are subject to, and qualified in their entirety by, such documents attached as Exhibits 10.1 and 10.2, respectively, to this Current Report on Form 8-K, which are incorporated herein by reference.