On January 30, 2023 Delcath Systems, Inc. (Nasdaq: DCTH), an interventional oncology company focused on the treatment of primary and metastatic cancers of the liver, reported that it will participate at the BTIG MedTech, Digital Health, Life Sciences, & Diagnostics Tools Conference in Snowbird, Utah on February 14 to 16 (Press release, Delcath Systems, JAN 30, 2023, View Source [SID1234626635]).

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Delcath CEO, Gerard Michel will be conducting one-on-one meetings. To request a one-on-one meeting please contact your BTIG representative with interest.

On January 30, 2023 C4 Therapeutics, Inc. (C4T) (Nasdaq: CCCC), a clinical-stage biopharmaceutical company dedicated to advancing targeted protein degradation science to develop a new generation of small-molecule medicines and transform how disease is treated, reported that the first patient has been dosed in its Phase 1/2 clinical trial of CFT1946, an orally bioavailable mutant-selective BiDAC degrader for the treatment of BRAF V600 mutant solid tumors (Press release, C4 Therapeutics, JAN 30, 2023, View Source [SID1234626634]).

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"Dosing the first patient in the CFT1946 Phase 1/2 clinical trial marks the first degrader to enter clinical development to target BRAF-driven cancers. Many of these patients are typically treated with BRAF inhibitors and have few treatment options once resistance emerges," said Adam Crystal, M.D., Ph.D., chief medical officer of C4 Therapeutics. "Preclinically, in in vivo models, CFT1946 has demonstrated deeper and more durable activity than approved BRAF inhibitors, and promising activity in the setting of resistance to BRAF inhibitors. We look forward to advancing CFT1946 for patients with BRAF V600 mutant cancers including non-small cell lung cancer, colorectal cancer, and melanoma."

The Phase 1/2 clinical trial will primarily investigate safety, tolerability, and anti-tumor activity, with secondary and exploratory objectives to characterize the pharmacokinetic and pharmacodynamic profile of CFT1946. The initial arm of the Phase 1 portion of the study will evaluate CFT1946 as a single agent in patients with BRAF V600 mutant solid tumors. As the Phase 1 trial progresses, an additional arm of the trial will evaluate CFT1946 in combination with trametinib, also in patients with BRAF V600 mutant solid tumors. Following the identification of the recommended dose(s), the Phase 2 portion of the trial is expected to expand to three investigational arms to evaluate: (1) CFT1946 monotherapy in patients with V600 mutant melanoma or non-small cell lung cancer (NSCLC) after prior BRAF inhibitor treatment; (2) CFT1946 in combination with trametinib in patients with V600 mutant melanoma or NSCLC after prior BRAF inhibitor treatment; and (3) CFT1946 in combination with trametinib in patients with V600 mutant NSCLC who have not previously been treated with a BRAF inhibitor.

CFT1946 is C4T’s third oncology program to enter clinical studies from its proprietary TORPEDO platform.

On January 30, 2023 Kite, a Gilead Company (NASDAQ: GILD), and Arcellx, Inc. (NASDAQ: ACLX), reported the closing of the companies’ previously reported global strategic collaboration to co-develop and co-commercialize Arcellx’s lead late-stage product candidate, CART-ddBCMA, for the treatment of patients with relapsed or refractory multiple myeloma (Press release, Arcellx, JAN 30, 2023, View Source [SID1234626633]). Multiple myeloma is an incurable disease for most patients and the need remains for effective, safe and broadly accessible therapies.

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Currently being investigated in a Phase 2 pivotal trial, CART-ddBCMA is Arcellx’s T-cell therapy utilizing the company’s novel synthetic binder, the D-Domain. Kite and Arcellx will jointly advance and commercialize the CART-ddBMCA asset in the U.S., and Kite will commercialize the product outside the U.S.

On January 30, 2023 Aptose Biosciences Inc. ("Aptose") (NASDAQ: APTO, TSX: APS) reported the 120 mg monotherapy dosing of patients in the APTIVATE Phase 1/2 clinical trial of tuspetinib (formerly HM43239), an oral, mutation agnostic tyrosine kinase inhibitor (TKI) being developed for the treatment of patients with relapsed or refractory acute myeloid leukemia (R/R AML) (Press release, Aptose Biosciences, JAN 30, 2023, View Source [SID1234626632]). In parallel, another clinical response has been achieved by a R/R AML patient receiving 40 mg tuspetinib once daily orally in the original dose exploration trial, the second response at the recently launched low-dose 40 mg cohort.

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Tuspetinib, a once daily oral agent designed to simultaneously target SYK, JAK1/2, FLT3, and other kinases operative in AML, has thus far as a monotherapy safely delivered multiple complete remissions and clinical responses across four dose levels (40mg, 80mg, 120mg, and 160mg) in AML patients that previously had been failed by chemotherapy, BCL2 inhibitors, hypomethylating agents, FLT3 inhibitors, and hematopoietic stem cell transplants. Data were presented last month at the 2022 American Society of Hematology (ASH) (Free ASH Whitepaper) annual meeting by lead investigator Naval G. Daver, M.D., Associate Professor in the Department of Leukemia at MD Anderson Cancer Center, showing tuspetinib delivers single agent responses without prolonged myelosuppression or life-threatening toxicities in these very ill and heavily pretreated relapsed or refractory AML patients. Responses were observed in a broad range of mutationally-defined populations, including those with mutated forms of NPM1, MLL, TP53, NRAS, KRAS, DNMT3A, RUNX1, wild-type FLT3, ITD or TKD mutated FLT3, various splicing factors, and other genes.

Importantly, Aptose has elucidated a rationale for the superior safety profile of tuspetinib. While several kinase inhibitors require high exposures that exert near complete suppression of a single target to elicit responses, those agents often cause additional toxicity because they also cause extensive inhibition of that target in normal cells. In contrast, tuspetinib simultaneously suppresses a small suite of kinase-driven pathways critical for leukemogenesis. Consequently, tuspetinib achieves clinical responses at lower exposures with less overall suppression of each pathway, thereby avoiding many of the toxicities observed with competing agents.

The APTIVATE expansion trial is designed to confirm monotherapy activity through patient enrichment of specific mutationally defined AML populations, including TP53-mutant patients and FLT3-mutant patients who have been failed by a prior FLT3 inhibitor, as supported by FDA fast-track designation and a clinically significant response rate to date. In the APTIVATE expansion trial, tuspetinib also will be tested in combination with venetoclax. More information on the APTIVATE trial can be found on www.clinicaltrials.gov (here).

"We are pleased to have dosing underway in our APTIVATE clinical trial of tuspetinib in a very ill R/R AML population," said William G. Rice, Ph.D., Chairman, President, and Chief Executive Officer. "Tuspetinib has demonstrated noteworthy safety and mutation agnostic potency across a spectrum of AML patients with a diversity of adverse mutations, further distinguishing it from competing compounds and targeting a much larger AML population. This breadth of activity along with its significant safety profile has allowed us to define a precise clinical and commercial plan for tuspetinib in multiple lines of therapy, including its use in doublet and triplet combinations, as well as maintenance therapy."

On January 30, 2023 Starpharma Holdings Limited (ASX: SPL, OTCQX: SPHRY) reported its Quarterly Activities Report and Appendix 4C for the period ended 31 December 2022 (Q2 FY23) (Press release, Starpharma, JAN 30, 2023, View Source;mc_eid=bf52dd3418 [SID1234626631]).

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Starpharma’s cash balance as at 31 December 2022 was $44.0 million, with a positive net operating cash flow of $2.2 million for the quarter. Total receipts of $8.1 million in the quarter include $7.1 million received from the Australian Government under its R&D tax incentive scheme[1] and receipts from customers of $1.0 million. Customer receipts, including from sales of VIRALEZE and VivaGel BV, were up 59% from the previous quarter (Q1 FY23: $0.6 million).

Partnered DEP Programs

During Q2 FY23, Starpharma announced preliminary AZD0466[2] safety and tolerability results from AstraZeneca’s ongoing Phase 1/2 clinical trial in patients with advanced relapsed/refractory leukemia (NCT04865419). The preliminary safety and tolerability results from 18 patients showed that AZD0466 was very well tolerated at multiple escalating dose levels (between 75 mg and 2400 mg), with no dose-limiting toxicities (DLTs) reported and no discontinuations due to treatment-related adverse events. The data showing increased patient numbers and significantly higher doses, with no DLTs, are significant in the context of the clinical trial. These preliminary results were presented by AstraZeneca at the American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting in December 2022. This Phase 1/2 clinical trial continues with further dose escalations planned. AstraZeneca is currently enrolling patients at 17 sites across the United States, Europe, Asia and Australia, with more than 30 sites expected to participate in the study.

AZD0466 is also the subject of a second Phase 1/2 clinical trial in patients with advanced non-Hodgkin lymphoma (NCT05205161). AstraZeneca is enrolling patients into this trial at six sites across the United States, Korea and Italy, with 18 additional sites planned.

Starpharma’s other partnered DEP programs with MSD, Genentech, and Chase Sun continued to progress well during the quarter. These partnered programs include DEP antibody drug conjugates (ADCs) and other DEP products across both oncology and anti-infectives. These and other DEP programs continue to be the subject of active discussions with Starpharma’s partners, including at the J.P. Morgan Healthcare Conference in January 2023. Meetings held at the JPM Conference included both new and existing partners.

Internal DEP Programs

Starpharma’s internal clinical DEP programs continue to advance, and are approaching completion of recruitment.

The DEP docetaxel clinical program continued to progress during the quarter, with 76 patients enrolled across the monotherapy and combination arms. The monotherapy arm is expected to complete recruitment within the next month, with the final patient now in screening. The DEP docetaxel and gemcitabine combination arm continues to recruit. Encouraging efficacy signals have been observed, including in heavily pre-treated patients with lung, pancreatic, oesophageal, cholangiocarcinoma and gastric cancers.

The DEP cabazitaxel Phase 2 trial has enrolled 76 patients to date, with the final patients with specific tumour types currently being screened and scheduled for treatment. Recruitment is expected to complete within the next 1-2 months. Data analyses and biostatistics activities are already underway. Starpharma has previously reported promising interim results from the prostate cancer cohort[3] of this trial. Other encouraging observations include significant tumour shrinkage and substantial tumour biomarker reductions in heavily pre-treated patients with advanced ovarian, gastro-oesophageal, cholangiocarcinoma, and head and neck cancers.

The DEP irinotecan Phase 2 trial continued to progress during the quarter, with 89 patients now recruited across both the monotherapy and combination arms. Final recruitment for the monotherapy arm is focused on platinum resistant ovarian cancer, where particularly encouraging responses have been observed, and is expected to complete within 2 months. Encouraging efficacy signals with DEP irinotecan have also been observed in heavily pre-treated patients with multiple other tumour types, including colorectal, breast, pancreatic, lung, and oesophageal cancers.

Starpharma continue commercial discussions with potential licensing partners for these internal DEP assets, as well as other commercial and collaborative discussions for other DEP programs and opportunities. Starpharma’s internal preclinical DEP programs, including DEP radiotheranostics and DEP ADCs, continue to progress in parallel.

Marketed Products

Soon after signing a sales and distribution agreement with Hengan[4]VIRALEZE nasal spray was launched in Hong Kong and Macau both online and in major pharmacy and retail outlets, Mannings; and PARKnSHOP, which is part of the A.S. Watson Group. The VIRALEZE rollout continues to be supported with marketing activities by Hengan, including advertising on television, newspapers and online platforms; billboards; and in-store promotion.

VIRALEZE sales and marketing activities also continue elsewhere, including in the UK, Italy, and Vietnam where Starpharma has distribution arrangements in place. In December 2022, Starpharma achieved VIRALEZE registration in Indonesia[5], a country with a population of more than 280 million. Starpharma continues to pursue registration and commercialisation activities for VIRALEZE in multiple other countries, with a focus on commercially attractive markets with rapid regulatory pathways. In Australia, the review by the Therapeutic Goods Administration (TGA) for the SPL7013 nasal spray as a medical device is ongoing.

New data generated by Scripps Research in the US on the efficacy of VIRALEZE against SARS-CoV-2 Omicron infection in an animal challenge model were presented at international virology conference, Respi DART[6], held in Mexico in December 2022[7]. In the study presented, VIRALEZE essentially eliminated SARS-CoV-2 Omicron virus (≥99.99% reduction in viral load compared with saline-treated animals) in the lung and trachea of virus-challenged animals, even when VIRALEZE was administered only after animals were exposed to virus. VIRALEZE-treated animals also exhibited significantly reduced proinflammatory cytokines compared with saline-treated animals; and achieved normal body weight gain compared to significant weight loss observed in saline-treated animals. Collectively, the results from this experiment indicate that VIRALEZE provides protection against SARS-CoV-2 infection and disease in animals challenged with the virus[8].

In December 2022, Starpharma commenced recruitment in the UK for a post-market clinical study of VIRALEZE. The study is enrolling patients with COVID-19 at Ashford and St Peter’s Hospitals NHS Foundation Trust (ASPH) in the UK. The post-market study will support ongoing marketing and commercial activities and will build on the positive in-market experience with the product.

Starpharma continues to work with its VivaGel BV partners, Mundipharma and Aspen. Further VivaGel BV registrations and product launches are planned in the Middle East and Philippines. Marketing campaigns by partners to build brand awareness and sales are ongoing, including for consumer and healthcare professional audiences.

Commenting on the Quarter’s highlights, Starpharma CEO, Dr Jackie Fairley, said:

"Starpharma continues to progress and drive value through its multiple internal and external DEP programs, including AZD0466, and its marketed product pipeline. We continue to maintain a strong cash position and were pleased to receive $7.1 million from the Federal Government’s R&D tax incentive scheme this quarter. Starpharma has continued to progress its multiple DEP partnerships with AstraZeneca, MSD, Genentech and Chase Sun. In parallel, Starpharma’s internal Phase 2 DEP trials are expected to complete recruitment soon, with only a handful of patients to be recruited into the monotherapy arms.

"It was exciting to attend the ASH (Free ASH Whitepaper) Meeting in December to hear firsthand the presentation of updated preliminary clinical data in relation to AZD0466, and to engage with AstraZeneca. AZD0466 is a novel dendrimer nanoparticle, which was developed under Starpharma’s multiproduct license with AstraZeneca. The preliminary results presented showed AZD0466 to be very well tolerated in patients with advanced relapsed/refractory leukemia, with no dose-limiting toxicities reported.

"Starpharma also continues to expand the sales and distribution of its antiviral nasal spray, VIRALEZE, with the product launched in Hong Kong and Macau and the registration of VIRALEZE in Indonesia during the quarter. Our post-market clinical study of VIRALEZE also commenced in the UK. This will support ongoing marketing and commercialisation of VIRALEZE."

"The Company looks forward to continuing this momentum and activity in calendar year 2023."

Cash Flows

Starpharma’s closing cash balance as at 31 December 2022 was $44.0 million, with net operating cash inflows of $2.2 million for the quarter. Total receipts of $8.1 million in the quarter includes $7.1 million received under the Australian Government’s R&D Tax Incentive scheme and receipts from customers of $1.0 million. Customer receipts include sales from VIRALEZE and VivaGel BV. R&D cash outflows of $2.6 million include clinical trial costs for Starpharma’s ongoing internal DEP clinical programs. Product manufacturing and operating costs were $0.9 million and include inventory and manufacturing costs related to the ongoing supply of VIRALEZE and VivaGel BV. Staffing costs were $2.6 million and include non-executive and executive directors’ fees of $442,000. Other related party transactions include $7,000 for consulting services to Centre for Biopharmaceutical Excellence Pty Ltd, which Starpharma non-executive director Dr Jeff Davies is also a director and shareholder. Cash outflows from investing activities of $0.4 million reflects investment in new scientific equipment for Starpharma’s laboratories.