On April 12, 2023 HUTCHMED (China) Limited ("HUTCHMED") (Nasdaq/AIM: HCM, HKEX: 13) reported that new and updated clinical and non-clinical data related to five HUTCHMED investigational drug candidates will be presented during the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2023 (AACR 2023), which will take place from April 14 to 19, 2023 in Orlando, Florida (Press release, Hutchison China MediTech, APR 12, 2023, View Source [SID1234629942]).

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Savolitinib

Title: A multicenter Phase II study of savolitinib in patients with MET-amplified gastroesophageal junction adenocarcinomas or gastric cancer
Lead Author: Lin Shen, MD, Peking University Cancer Hospital & Institute
Type: Poster presentation
Session Number: PO.CT02.01 – Phase II Clinical Trials 1
Abstract Link: View Source!/10828/presentation/10376

Title: Baseline and on-treatment plasma-based genomics as a predictor of outcome in SAVANNAH: Savolitinib + osimertinib in EGFRm MET overexpressed/​amplified NSCLC post-osimertinib
Lead Author: Ryan J Hartmaier, Ph.D, AstraZeneca
Type: Poster presentation
Session Number: LB294/7
Abstract Link: View Source!/10828/presentation/9996

Mesenchymal epithelial transition factor ("MET") gene amplification is associated with poor prognosis in gastric cancer ("GC") and gastroesophageal junction adenocarcinomas ("GEJ"). Savolitinib is a potent and highly selective oral MET tyrosine-kinase inhibitor.

Here we reported the preliminary efficacy and safety data from a Phase II trial of savolitinib monotherapy in patients with MET-amplified advanced or metastatic GC/GEJ (NCT04923932). Additionally, utility of plasma-based genomics was investigated in the SAVANNAH Phase II trial of savolitinib in addition to osimertinib in epidermal growth factor receptor (EGFR) mutated, MET overexpressed/amplified non-small cell lung cancer ("NSCLC") post osimertinib. First presentation of the SAVANNAH results occurred at the International Association for the Study of Lung Cancer (IASLC) 2022 World Conference on Lung Cancer (WCLC) in August 2022.

Surufatinib

Title: Surufatinib plus toripalimab for first-line treatment of advanced non-small cell lung cancer (NSCLC) with PD-L1 positive expression: A multicenter, single-arm phase 2 study
Lead Author: Ying Cheng, MD, Jilin Cancer Hospital
Type: Poster presentation
Session Number: PO.CT02.02 – Phase II Clinical Trials 2
Abstract Link: View Source!/10828/presentation/10405

Surufatinib (a small-molecule inhibitor of vascular endothelial growth factor receptor ("VEGFR") 1-3, fibroblast growth factor receptor ("FGFR") 1 and colony-stimulating factor 1 receptor ("CSF-1R")) plus toripalimab (an anti-programmed cell death protein-1 ("PD-1") antibody) showed encouraging antitumor activity in solid tumors. Programmed death ligand 1 ("PD-L1") expression is the established biomarker for first-line immune checkpoint inhibitors therapy in advanced NSCLC. We conducted an open-label, multi-cohort, single-arm Phase II study to evaluate the safety and efficacy of surufatinib plus toripalimab in patients with advanced solid tumors. Here, we reported the results of advanced NSCLC with PD-L1 positive expression cohort (NCT04169672).

HMPL-760

Title: HMPL-760 is a highly potent and selective reversible BTK inhibitor, targeting BTK and BTKC481S in B-cell malignancies
Lead Author: Linfang Wang, HUTCHMED
Type: Poster presentation
Session Number: PO.ET09.07 – Tyrosine Kinase and Phosphatase Inhibitors 1
Abstract Link: View Source!/10828/presentation/6728

Bruton’s tyrosine kinase ("BTK"), a member of the Tec family, plays a crucial role in signaling through B-cell receptor ("BCR"). BTK inhibition blocks BCR signals and prevents B-cell activation and growth. First-generation BTK inhibitors such as ibrutinib covalently binds to a cysteine residue ("C481") of BTK. Their most frequent acquired resistance is the development of a serine mutation in the binding site ("C481S"). Next generation BTK inhibitors such as HMPL-760 aim to overcome this resistance to first-generation inhibitors.

The poster outlined preclinical data showing HMPL-760 is a reversible, selective, highly potent BTK inhibitor targeting both BTKWT and BTKC481S. The first-in-human Phase I clinical trials of HMPL-760 are under way in patients with relapsed/refractory B-Cell Non-Hodgkin’s Lymphoma (NCT05190068).

HMPL-306

Title: Preclinical characteristic of HMPL-306, a CNS-penetrable dual inhibitor of mutant IDH1 and IDH2
Lead Author: Na Yang, HUTCHMED
Type: Poster presentation
Session Number: PO.ET01.01 – Oncogenes and Tumor Suppressor Genes as Targets for Therapy 1
Abstract Link: View Source!/10828/presentation/8579

Mutations in isocitrate dehydrogenase ("IDH") 1/2 are frequently identified in various cancers, such as acute myeloid leukemia ("AML"), cholangiocarcinoma, chondrosarcoma and glioma. Mutant IDHs ("mIDHs") cause accumulated 2-hydroxyglutarate, leading to blockage of cell differentiation, thereby inducing malignant transformation. Rare cases were identified carrying co-existing mutations in IDH1 and IDH2. mIDH isoform switching, from mutant IDH1 to mutant IDH2 and vice versa, have been reported as a mechanism of acquired resistance to IDH inhibition in AML and cholangiocarcinoma. Thus, simultaneous inhibition on both mIDH1 and mIDH2 may be a promising strategy to overcome resistance and improve clinical efficacy. HMPL-306, a dual inhibitor of mIDH1/mIDH2, developed by HUTCHMED, is being evaluated in clinical trials ().

The poster outlines preclinical data that shows that HMPL-306 is a potent, durable, dual inhibitor of IDH1/2 mutation that crosses the blood brain barrier and demonstrated effect on pharmacodynamic markers that lead to the differentiation of immature malignant cells to mature normal cells. The strong activity and favorable pharmacokinetics profiles support further clinical evaluation.

HMPL-453

Title: HMPL-453, a highly selective inhibitor of fibroblast growth factor receptors 1, 2, and 3, displays potent activity in FGFR-altered tumor models
Lead Author: Jia Hu, HUTCHMED
Type: Poster presentation
Session Number: PO.ET01.07 – Growth Factor Receptors as Therapeutic Targets
Abstract Link: View Source!/10828/presentation/8706

Fibroblast growth factors ("FGFs") and their receptors ("FGFRs") regulate numerous cellular processes. Dysregulation of FGFR signaling due to receptor fusion, mutation or amplification is observed across multiple cancer types, making activated FGFRs an important therapeutic target. Herein, we presented the preclinical characterization of HMPL-453, a highly potent and selective inhibitor of FGFR1, 2, and 3, discovered and being currently developed in Phase II clinical trial (NCT04353375) by HUTCHMED.

The presentation outlines preclinical data that shows that HMPL-453 is a highly potent and selective inhibitor of FGFR 1, 2, and 3 with strong activity against FGFR-deregulated tumors in preclinical models, supporting continued investigation in patients with FGFR alterations (such as fusion and mutation) either as a single agent or in combination with PD-1 blockade.

About Savolitinib (ORPATHYS in China)
Savolitinib is an oral, potent and highly selective MET tyrosine kinase inhibitor that has demonstrated clinical activity in advanced solid tumors. Іt blocks atypical activation of the MET receptor tyrosine kinase pathway that occurs because of mutations (such as exon 14 skipping alterations or other point mutations), gene amplification or protein overexpression.

Іn 2011, AstraZeneca and HUTCHMED entered a global licensing and collaboration agreement to jointly develop and commercialize savolitinib. Joint development of savolitinib in China is led by HUTCHMED, while AstraZeneca leads development outside of China. HUTCHMED is responsible for the marketing authorization, manufacturing and supply of savolitinib in China. AstraZeneca is responsible for the commercialization of savolitinib in China and worldwide. Sales of savolitinib are recognized by AstraZeneca.

About Surufatinib (SULANDA in China)
Surufatinib is a novel, oral angio-immuno kinase inhibitor that selectively inhibits the tyrosine kinase activity associated with VEGFR and FGFR, which both inhibit angiogenesis, and CSF-1R, which regulates tumor-associated macrophages, promoting the body’s immune response against tumor cells. Its unique dual mechanism of action may be very suitable for possible combinations with other immunotherapies, where there may be synergistic anti-tumor effects.

HUTCHMED currently retains all rights to surufatinib worldwide.

About HMPL-760
HMPL-760 is an investigational, non-covalent, third-generation BTK inhibitor. It is a highly potent, selective, and reversible inhibitor against both wild-type and C481S-mutated BTK.

HUTCHMED currently retains all rights to HMPL-760 worldwide.

About HMPL-306
HMPL-306 is a novel dual-inhibitor of ꞮDH1 and ꞮDH2 enzymes. ꞮDH1 and ꞮDH2 mutations have been implicated as drivers of certain hematological malignancies, gliomas and solid tumors, particularly among acute myeloid leukemia patients.

HUTCHMED currently retains all rights to HMPL-306 worldwide.

About HMPL-453
HMPL‑453 is a novel, highly selective and potent inhibitor targeting FGFR 1, 2 and 3. Aberrant FGFR signaling has been found to be a driving force in tumor growth (through tissue growth and repair), promotion of angiogenesis and resistance to anti-tumor therapies. Abnormal FGFR gene alterations are believed to be the drivers of tumor cell proliferation in several solid tumor settings.

HUTCHMED currently retains all rights to HMPL-453 worldwide.

On April 11, 2023, NovAccess Global Inc. ("NovAccess" or the "company") entered into a securities purchase agreement (the "SPA") with 1800 Diagonal Lending LLC ("1800 Diagonal Lending") and issued a convertible promissory note in the original principal amount of $79,250 (the "note") to 1800 Diagonal Lending pursuant to the SPA (Filing, 8-K, NovAccess Global, APR 11, 2023, View Source [SID1234630251]). The loan funded on April 14, 2023. NovAccess will use the proceeds of the loan for general working capital purposes.

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NovAccess provided typical representations and agreed to standard covenants pursuant to the SPA. The SPA does not include any financial covenants.

The note bears interest at 8% a year and is due on April 11, 2024. NovAccess may prepay the note upon payment of a prepayment penalty ranging from 15-25% of the amount outstanding on the note when prepaid. Under the terms of the note, NovAccess may not sell a significant portion of its assets without the approval of 1800 Diagonal Lending, must comply with the company’s reporting requirements under the Securities Exchange Act of 1934, and must maintain the listing of the company’s common stock on the OTCQB Market or other exchange. NovAccess’ failure to comply with any of these covenants, among other matters, would constitute an event of default. Upon an event of default, the note will bear interest at 22% and 1800 Diagonal Lending will be entitled to its costs of collection.

Beginning on October 8, 2023, 1800 Diagonal Lending may convert the amount outstanding under the note into shares of NovAccess common stock at a conversion price equal to 65% of the average of the three lowest trading prices of the stock during the fifteen trading days before the conversion date.

The SPA and note are filed as exhibits to this Current Report on Form 8-K. The descriptions above are qualified in their entirety by reference to the full text of these documents.

On April 11, 2023 LAVA Therapeutics N.V. (Nasdaq: LVTX), a clinical-stage immuno-oncology company focused on developing its proprietary Gammabody platform of bispecific gamma-delta T cell engagers, reported recent corporate highlights and financial results for the fourth quarter and year ended December 31, 2022 (Press release, Lava Therapeutics, APR 11, 2023, View Source [SID1234629997]).

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"2022 was a very productive year for LAVA, marked by steady progress in the clinical development of our lead programs, LAVA-051 and LAVA-1207," said Stephen Hurly, president and chief executive officer of LAVA Therapeutics. "We are encouraged by the initial safety and activity signals and will continue dose escalation in these programs as we work toward a recommended Phase 2 dose. We will also continue to advance our pipeline of bispecific gamma-delta T cell engagers for patients with cancer."

"On the corporate front, we strengthened our management team with the additions of two seasoned executives, Dr. Charles Morris as chief medical officer and Fred Powell as chief financial officer. Both executives joined LAVA following several decades of experience and proven track records of success in their prior roles. The Company also appointed three highly accomplished independent members to the Board of Directors, which reflects an important progression in the Company’s evolution," continued Hurly.

Recent Pipeline Highlights

LAVA-051

Gammabody designed to target CD1d-expressing tumors, including multiple myeloma (MM), chronic lymphocytic leukemia (CLL) and acute myeloid leukemia (AML)

● Initial clinical data for LAVA-051 and presented clinical pharmacokinetic and pharmacodynamic data from the first five patient cohorts of the Phase 1 dose-escalation study that suggest a favorable safety profile, which allowed us to expand the enrollment of patients into planned additional cohorts.
● Potential signs of clinical activity were observed as well as linear PK and on-mechanism PD parameters consistent with Vγ9Vδ2-T cell engagement.
● Clinical trial sites are actively enrolling in North America and Europe.

LAVA-1207

Gammabody designed to target the prostate-specific membrane antigen (PSMA) to trigger the potent and preferential killing of PSMA-positive tumor cells in patients with metastatic castration-resistant prostate cancer (mCRPC)

● Initial clinical data suggests a favorable safety profile, with no occurrence of high-grade (>2) cytokine release syndrome.
● Initial signs of anti-tumor activity were observed, with iRECIST stable disease (iSD) in 8 out of 14 evaluable patients at week 8 and PSA levels stabilizing or decreasing in heavily pre-treated patients.
● Clinical trial sites are actively enrolling in sites in North America and Europe.

Corporate Update

● LAVA strengthened its executive management team with the following appointments:
o Dr. Charles Morris was appointed as chief medical officer. Dr. Morris is a medical oncologist with over 25 years of oncology drug development experience and has a proven track record of advancing novel oncology product candidates from clinical development through global regulatory approvals.
o Fred Powell was appointed chief financial officer and brings over 25 years of experience as a global CFO in the biopharmaceutical industry, having served in this capacity for several publicly traded biopharmaceutical companies.
o Three new independent directors were appointed to the LAVA Board of Directors: Peter A. Kiener, DPhil, Mary Wadlinger and Christy Oliger. Guido Magni, M.D., Ph.D., and Stefan Luzi, Ph.D., stepped down from the Board.

● In September 2022, we announced an exclusive global license agreement with Seagen pursuant to which we granted a worldwide exclusive license to Seagen to develop, manufacture and commercialize SGN-EGFRd2 (LAVA-1223), an advanced preclinical

asset that utilizes LAVA’s proprietary Gammabody technology to target EGFR-expressing solid tumors. Under the terms of the agreement, LAVA received a $50 million upfront payment and could receive up to approximately $650 million in potential development, regulatory and commercial milestones, and royalties ranging from the high single digits to the mid-teens on future sales.

Fourth Quarter and Year-End 2022 Financial Results

The financial information provided below reflects changes made to previously issued consolidated financial statements to revise immaterial prior period misstatements. Further information regarding the revision is included in our consolidated financial statements, "Note 23 — Revision of Immaterial Misstatements," included in Item 18 of our annual report on Form 20-F.

● As of December 31, 2022, LAVA had cash, cash equivalents and investments totaling $132.9 million compared to cash and cash equivalents of $133.2 million as of December 31, 2021. The cash balance is expected to be sufficient to fund the Company’s activities into 2026.
● Research and license revenue was $2.6 million and $1.1 million for the quarters ended December 31, 2022 and 2021, respectively, and $19.4 million and $5.4 million for the years ended December 31, 2022 and 2021, respectively. The full-year increase was primarily due to $17.9 million in revenue from the Company’s collaboration with Seagen Inc.
● Research and development expenses were $10.5 million and $6.6 million for the quarters ended December 31, 2022 and 2021, respectively, and $40.1 million and $36.9 million for the years ended December 31, 2022 and 2021, respectively. The higher quarterly and full-year expense was due to ongoing activities of the clinical trials for LAVA-051 and LAVA-1207, which were offset by a one-time license fee of $14.4 million triggered in the first quarter of 2021 by the IPO.
● General and administrative expenses were $3.7 million and $3.8 million for the quarters ended December 31, 2022 and 2021, respectively, and $14.1 million and $12.0 million for the years ended December 31, 2022 and 2021, respectively. The increase for the full year 2022 was due to higher personnel-related expenses and the costs of being a public company for a full year compared to only 9 months in 2021.
● Net losses were $15.0 million and $8.2 million for the quarters ended December 31, 2022 and 2021, respectively, or $0.57 and $0.32 net loss per share for the quarters ended December 31, 2022 and 2021, respectively, and $31.9 million and $42.4 million for the years ended December 31, 2022 and 2021, respectively, or $1.23 and $2.14 net loss per share for the years ended December 31, 2022 and 2021, respectively.

On April 11, 2023 MAIA Biotechnology, Inc. (NYSE American: MAIA) reported positive topline data from the completed Part A safety lead-in of the Company’s THIO-101 Phase 2 go-to-market trial in advanced Non-Small Cell Lung Cancer (NSCLC) and has commenced recruitment in Part B randomized efficacy/dose selection (Press release, MAIA Biotechnology, APR 11, 2023, View Source [SID1234629981]).

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Topline data from Part A demonstrated that MAIA’s telomere-targeting agent, THIO, administered in sequential combination with Regeneron’s anti-PD-1 therapy, Libtayo (cemiplimab), were generally well-tolerated. No dose-limiting toxicities (DLTs) or significant treatment-related adverse events were observed.

Part A was designed to assess the safety and tolerability of the highest dose of 360 mg/cycle in six patients. Mild toxicities, such as grade 1 fatigue, and muscle pain, were reported, as well as only one occurrence of grade 3 nausea, but no grade 4 adverse events, reported.

"Part A’s safety profile is in sharp contrast with the typical safety profile of chemotherapy treatment where 70-80% of NSCLC patients experience grade 3 and 4 toxicities," said MAIA’s Chief Medical Officer Mihail Obrocea, M.D. "The next dose levels of THIO in Part B are lower compared to Part A. Based on the initial safety profile seen at the highest dose in Part A, we are optimistic about the safety profile of THIO."

"We are pleased with the completion of the safety lead-in portion, which is a very important milestone and catalyst that marks the continued progression of our Phase 2 THIO-101 trial. Recruitment has commenced in the Part B efficacy/dose selection portion of our go-to-market trial, and we anticipate reporting preliminary efficacy data later this year," said MAIA’s Chairman and Chief Executive Officer Vlad Vitoc, M.D.

Part B of the study will allow randomization of patients to three THIO dose levels, including 60 mg, 180 mg and 360 mg, followed by cemiplimab treatment every 3 weeks. Safety and tolerability will continue to be monitored across all THIO doses. The objective of Part B is to determine the most efficacious and safe dose, which will guide Part C of the trial.

THIO-101 is a multicenter, open-label, dose-finding Phase 2 clinical trial designed to evaluate THIO’s potential direct anticancer and immune system activation effects in NSCLC patients by administering THIO in advance of Regeneron’s anti-PD-1 therapy, Libtayo (cemiplimab), thus allowing for immune system activation and sensitivity to the PD-1 inhibitor to take effect. The primary objectives of the trial are to evaluate the safety and tolerability of THIO administered as a direct anti-cancer and priming immune system agent followed by cemiplimab administration, as well as preliminary clinical efficacy of THIO in patients with advanced NSCLC, who either progressed or relapsed through the initial treatments with an immune-check point inhibitor alone, or in combination with chemotherapy. The clinical trial is currently enrolling patients in Australia and the European Union. For more information on this Phase II trial, please visit ClinicalTrials.gov using the identifier NCT05208944.

About Toxicity Grading in Cancer Treatments

Toxicity is graded 0-5. Toxicity of grade 1 is mild, grade 2 is moderate, grade 3 is severe, grade 4 is life-threatening, and grade 5 is death.

About THIO

THIO (6-thio-dG or 6-thio-2’-deoxyguanosine) is a telomere-targeting agent currently in clinical development to evaluate its activity in non-small cell lung cancer (NSCLC), in sequential administration with Regeneron’s anti-PD-1 therapy, Libtayo (cemiplimab). Telomeres play a fundamental role in the survival of cancer cells and their resistance to current therapies. THIO is being developed as a second or later line of treatment for NSCLC for patients that have progressed beyond the standard-of-care regimen of existing checkpoint inhibitors.

On April 11, 2023 Puma Biotechnology, Inc. (NASDAQ: PBYI), a biopharmaceutical company, reported that on April 8, 2023, the Compensation Committee of Puma’s Board of Directors approved the grant of inducement restricted stock unit awards covering 22,000 shares of Puma common stock to four new non-executive employees (Press release, Puma Biotechnology, APR 11, 2023, View Source [SID1234629980]).

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The awards were granted under Puma’s 2017 Employment Inducement Incentive Award Plan, which was adopted on April 27, 2017 and provides for the granting of equity awards to new employees of Puma. The restricted stock unit awards vest over a three-year period, with one-third of the shares underlying each award vesting on the first anniversary of the award’s vesting commencement date, April 1, 2023, and one-sixth of the shares underlying each award vesting on each six-month anniversary of the vesting commencement date thereafter, subject to continued service. The awards were granted as an inducement material to the new employees entering into employment with Puma, in accordance with Nasdaq Listing Rule 5635(c)(4).