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.

On January 30, 2023 Immutep Limited (ASX: IMM; NASDAQ: IMMP) ("Immutep" or "the Company"), a biotechnology company developing novel LAG-3 related immunotherapy treatments for cancer and autoimmune diseases, reported an update on the ongoing development of its product candidates, efti and IMP761, for the quarter ended 31 December 2022 (Q2 of Fiscal Year 2023) (Press release, Immutep, JAN 30, 2023, View Source [SID1234626629]).

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EFTI DEVELOPMENT PROGRAM FOR CANCER

Planned late-stage trial in 1L NSCLC
The United States Food and Drug Administration (US FDA) granted Fast Track designation to efti in combination with pembrolizumab in October 2022 for the treatment of 1L NSCLC, which will be evaluated in the Company’s planned late-stage registrational trial. The designation was granted based on the encouraging Phase II clinical data in 1L NSCLC from the TACTI-002 all-comer trial in terms of PD-L1 status, presented at American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper)’s (ASCO) (Free ASCO Whitepaper) Annual Meeting in June 2022. It is the second Fast Track designation issued by the FDA for efti (the first is for 1L HNSCC) and offers the potential for expedited development and review.

TACTI-002 (also designated KEYNOTE-PN798) Phase II clinical trial

Immutep reported compelling new clinical data from the TACTI-002 trial evaluating efti in combination with MSD’s (Merck & Co., Inc., Rahway, NJ., USA) anti-PD-1 therapy KEYTRUDA (pembrolizumab) in 1L NSCLC via a late-breaking abstract oral presentation at the Society of Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) Meeting in November 2022. Immutep’s abstract was one of just nine to be showcased at the SITC (Free SITC Whitepaper) 2022 press briefing, out of more than 1,500 abstract submissions.

The results showed an ORR of 40.4% in the all-comer PD-L1 trial, meeting the primary endpoint of the 1L NSCLC part of the trial. The ORR improved across all PD-L1 status groups by central assessment compared with data reported at ASC0 2022. Additionally, the interim median Duration of Response (DoR) of 21.6 months, compares favourably to historical controls. Promising results were also achieved in the secondary endpoint of interim median Progression Free Survival (PFS) with overall PFS of 6.6 months and 9.3 months in patients with a PD-L1 TPS (Tumour Proportion Score) >1% for which efti in combination with pembrolizumab has Fast Track designation.

TACTI-003 – Phase IIb clinical trial

In October 2022, the IDMC for Immutep’s Phase IIb TACTI-003 trial reviewed the initial safety data from the study and recommended the trial continue with no modifications. The IDMC also reviewed initial efficacy data, although this was not the primary focus of the analysis. The recommendation validates Immutep’s decision to evaluate efti in the 1st line HNSCC setting following an encouraging ORR of 29.7% regardless of PD-L1 expression and five complete responses (CR) reported in the 2nd line HNSCC setting in TACTI-002.

The Company also presented a Trial in Progress poster on the TACTI-003 study at the SITC (Free SITC Whitepaper) 2022 meeting in November 2022. Recruitment is ongoing for the TACTI-003 trial, with more than 50% of the planned 154 patients enrolled till quarter end.

Planned Phase II/III trial in Metastatic Breast Cancer

Immutep reported the positive outcome of its follow-up Type C meeting with the US FDA regarding its latestage clinical development plans for efti in conjunction with standard-of-care chemotherapy for the treatment of MBC in December 2022. The Company and the FDA have agreed to an integrated Phase II/III trial design to help inform a Biologics License Application (BLA).

Based on the encouraging efficacy, favourable safety and learnings from the randomised AIPAC Phase IIb trial (which administered efti and chemotherapy on different days and ceased chemotherapy at six months), patients will receive efti and paclitaxel on the same day and treatment will continue until disease progression. In addition to HER2–/HR+ metastatic breast cancer, the patient population has also been expanded to include triple-negative breast cancer (TNBC), an aggressive form of breast cancer with limited treatment options.

Subject to regulatory and ethics committee feedback, the Phase II portion of the trial is expected to begin in Q3 FY23 with a safety lead in of 6 to 12 patients who will be given a higher 90mg dose of efti (compared to the completed AIPAC trial). This will be followed by 58 patients for the randomised Phase II portion of the trial. Depending on the Phase II results and Immutep’s resources, the Phase III portion will commence.

Phase II trial in Soft Tissue Sarcoma

Trial preparations continued during the quarter for a new investigator-initiated Phase II clinical trial which was announced in September 2022. The trial will be conducted in collaboration with the Maria SkłodowskaCurie National Research Institute in Poland and will evaluate efti in combination with pembrolizumab and radiotherapy, prior to surgery, in up to 40 patients with select soft tissue sarcoma. The trial is expected to commence in H1 of calendar year 2023.

INSIGHT-003 – Phase I triple combination with standard-of-care anti-PD-1 therapy and chemotherapy

Initial clinical data was reported from the investigator-initiated INSIGHT-003 trial in November at the SITC (Free SITC Whitepaper) 2022 conference. The poster provided initial efficacy details on 11 of the 14 patients with metastatic NSCLC adenocarcinomas that had been enrolled as of the 14 October 2022 cut-off date, plus safety data on all 14 patients. The data shows the triple-combination approach is well-tolerated and provides promising early signals of therapeutic activity with an ORR of 72.7% (8/11) and a Disease Control Rate (DCR) of 90.9% (10/11).

INSIGHT-005 – New Phase I trial with Merck KGaA, Darmstadt, Germany, and Pfizer

Immutep signed a Clinical Trial Collaboration and Supply Agreement with Merck KGaA, Darmstadt, Germany and Pfizer in November 2022 for a new Phase I clinical study in patients with urothelial cancer, called INSIGHT005. It is the second agreement entered into by Immutep with Merck KGaA and Pfizer and builds on the encouraging clinical data reported from the completed INSIGHT-004 study in multiple solid tumour indications from efti and avelumab (BAVENCIO). Under the Agreement, Immutep and Merck KGaA will jointly fund the study, which is expected to start in mid-calendar year 2023.

Efti Manufacturing Scale-Up

Immutep successfully scaled-up the manufacturing process for efti with the completion of its first 2,000L manufacturing run by the Company’s manufacturing partner, WuXi Biologics. This large-scale manufacturing capability is a significant achievement. Immutep plans to introduce the material manufactured into ongoing and future Phase II/III clinical trials.

IMP761 DEVELOPMENT PROGRAM FOR AUTOIMMUNE DISEASES

During the quarter, Immutep established a GMP-compliant manufacturing processfor IMP761, its proprietary preclinical candidate for autoimmune diseases. The 200L scale manufacturing process was developed by the Company’s manufacturing partner, Northway Biotech and will provide supply of IMP761 for Investigational New Drug (IND)-enabling studies and clinical trials.

INTELLECTUAL PROPERTY

Immutep was granted four new patents during the quarter. The first two patents were filed as divisional applications and were granted by the Japanese and South Korean Patent Offices. These patents protect Immutep’s intellectual property relating to combination preparations comprising efti and a chemotherapy agent which is oxaliplatin, carboplatin, or topotecan. They follow the grant of the Japanese parent patent and corresponding patentsin the United States, Europe, China and Australia, as announced in 2019 through 2021. The Company was granted another patent by the South Korean Patent Office, which relates to a potency assay for release testing of efti. The assay is used in Immutep’s commercial-scale (2,000L) manufacturing process.

Immutep was also granted a new patent by the Chinese Patent Office. The patent protects IMP731 in the territory of mainland China. The patent is co-owned with the French Institute of Health and Medical Research (INSERM) and exclusively licensed to GSK, Immutep’s development partner for IMP731.

FINANCIAL SUMMARY

Immutep’s financial performance over the quarter (Q2 FY23) continues to reflect prudent cash management. The Company’s cash runway was expanded to the end of FY24 (previously early H2 FY24).

Cash receipts from customers Q2 FY23 were $8k, compared to $33k in Q1 FY23. The Company received a A$986,286 cash rebate from the Australian Federal Government’s R&D tax incentive program in relation to expenditure incurred on eligible R&D activities conducted in Australia in the 2021 fiscal year.

The net cash used in G&A activities in the quarter was $734k compared to $595k in Q1 FY23.

Payments to Related Parties, detailed in Item 6 of the Appendix 4C cash flow report for the quarter, includes $402k in payment of Non-Executive Director’s fees and Executive Director’s remuneration.

The net cash used in R&D activities in the quarter was $5.87 million, compared to $7.17 million in Q1 FY23. The decrease was mainly due to a reduction in manufacturing activities during the quarter.

Total net cash outflows used in operating activities in the quarter were $7.02 million compared to $6.35 million in Q1 FY23.

Immutep’s cash and cash equivalent balance at 31 December 2022 was approximately $68.38 million, giving the Company an expected cash reach based on current estimates to the end of FY24. Immutep will continue to manage its strong cash balance carefully as it pursues its overall clinical development strategy.

A copy of the Appendix 4C-Quarterly Cash Flow Report for the quarter is attached.

On January 30, 2023 Amplia Therapeutics Limited (ASX: ATX), ("Amplia" or the "Company"), a company developing new drug candidates for the treatment for cancer and fibrosis, reported further progress across its small molecule, focal adhesion kinase (FAK) inhibitor program and the release of its Appendix 4C Cash Flow Report (attached) for the quarter ending 31 December 2022 (Press release, Amplia Therapeutics, JAN 30, 2023, View Source [SID1234626628]).

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Key Highlights from the Quarter

• Completion of recruitment of first cohort of patients into ACCENT Phase 2 clinical trial of AMP945 in pancreatic cancer;
• Encouraging data for AMP886 in a preclinical model of Acute Myeloid Leukemia (AML);
• Dr Christopher Burns appointed as CEO.

Operations Update
Clinical Development
During the Quarter, Amplia announced completion of enrolment of the first cohort of patients in the Company’s Phase 1b/2a ACCENT clinical trial of focal adhesion kinase inhibitor AMP945. The trial tests whether AMP945 enhances the efficacy of gemcitabine/nab-paclitaxel standard-of-care chemotherapy in frontline patients with advanced pancreatic cancer.

By the end of 2022, seven sites in Melbourne, Sydney and Brisbane had been opened to recruit patients into the ACCENT trial. To help raise the profile of the trial amongst pancreatic cancer specialists and oncologists, the company sponsored and attended the Australasian Gastro-Intestinal Trials Group (AGITG) Annual Scientific Meeting in Melbourne in November.

Non-clinical Development

Studies completed during the Quarter also showed that AMP886, Amplia’s second FAK inhibitor, may have utility in the treatment of acute myeloid leukemia (AML). In addition to inhibiting FAK, AMP886 also potently blocks activity of the two related kinases FLT3 and VEGFR3. The company has now shown that AMP886 inhibits AML in an industry-standard MV4-11 disease model carrying a common mutation in FLT3. Patients whose disease carries this mutation often have more rapid progression and significantly worse prognosis. Furthermore, in this model AMP886 enhances the efficacy of venetoclax, a drug approved to treat AML as part of combination therapy. Additional studies exploring the potential of AMP886 in AML and other cancers are underway.

Management

Dr Christopher Burns was appointed as CEO and Managing Director of Amplia Therapeutics on 5th December. Dr Burns was a founder of Amplia Therapeutics and has been a Board member since May 2018.

Financial update

Amplia finished the December 2022 quarter with cash of $10.6 million (September 2022: $11.7 million). During the quarter, the Company had net cash outflows of $1.1 million in relation to operating activities (September 2022: $1.1 million).
Operating cashflows included outflows and inflows of:
• $0.7 million for staff and administration/corporate costs; and
• $0.5 million for research and development costs, which primarily related to Contract Research Organisation (CRO), manufacturing and other CMC related costs incurred in relation to the first stage of the Phase 2 clinical trial for AMP945. Research and development expenditure is forecast to increase in the coming quarters in line with the progression of Phase 1b/2a of the ACCENT clinical trial for AMP945.

Payments to Related Entities

In accordance with Listing Rule 4.7C, payments made to related parties and their associates included in item 6.1 of the Appendix 4C incorporates directors’ fees, salaries and superannuation. Total payments made for the quarter equals $172,929 and relate to payments to the CEO/Managing Director’s in line with employment contracts and payments to the Non-Executive Directors. Outlook and future activities In the coming quarter, the Company expects to report further progress in the ACCENT trial including updates on progression towards optimal dose selection. Work on a regulatory submission to South Korea is well advanced which, if approved, will allow sites to be opened that should further enhance recruitment rate.

Studies continue on the novel metabolite of AMP945 identified in samples from the Phase 1 clinical trial. The presence of the metabolite is not anticipated to impact timelines for the pancreatic cancer trial currently underway.

Non-clinical studies of Amplia’s second FAK inhibitor, AMP886, are ongoing to identify the best clinical opportunities for this compound. Additional non-clinical studies with AMP945 are also underway to explore and support clinical application of the drug in other oncology and non-oncology indications. Data generated from these studies will be communicated as they are received.

This ASX announcement was approved and authorised for release by the Board of Amplia Therapeutics.

On January 29, 2021 Amgen reported that its investigational KRASG12C inhibitor sotorasib was granted Breakthrough Therapy Designation (BTD) by the Center for Drug Evaluation (CDE) of the National Medical Products Administration (NMPA) (Press release, Amgen, JAN 29, 2023, View Source [SID1234633506]). The designation is for the treatment of patients with KRAS G12C-mutated locally advanced or metastatic non-small cell lung cancer (NSCLC) who have received at least one prior systemic therapy. This is the first BTD submission for Amgen in China, as well as the first under Amgen’s strategic collaboration with BeiGene.

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NSCLC is the most common form of lung cancer, accounting for approximately 80-85% of all cases worldwide.1 KRAS G12C is the most common KRAS mutation in NSCLC.2,3 The mutation is a biomarker of poor prognosis in Chinese NSCLC patients, which may be improved by G12C-specific inhibitors.4 Research has shown that about 3-5% have the KRAS G12C mutation – found most commonly in smokers.4,5

"Given that Breakthrough Therapy Designation is a new pathway in China, we are pleased to receive this designation for sotorasib," said David M. Reese, M.D., executive vice president of Research and Development at Amgen. "This designation underscores the importance of sotorasib and we look forward to working with regulatory authorities in China to bring the first potential targeted therapy to NSCLC patients with the KRAS G12C mutation."

The Breakthrough Therapy Designation is supported by the positive CodeBreaK 100 Phase 2 results in patients with advanced NSCLC whose cancer had progressed despite prior treatment with chemotherapy and/or immunotherapy. In the study, treatment with sotorasib demonstrated durable anticancer activity with a positive benefit-risk profile.6 These results will be presented at the International Association for the Study of Lung Cancer (IASLC) 2020 World Conference on Lung Cancer (WCLC) Presidential Symposium from 3:50-4 p.m. PST on Friday, Jan. 29.

The NMPA’s BTD process is designed to expedite the development and review of therapies that are intended for the prevention or treatment of serious life-threatening diseases for which there is no existing treatment and where preliminary evidence indicates advantages of the therapy over available treatment options.7 This designation shows the potential for sotorasib to become the first targeted treatment available in China for KRAS G12C-mutated NSCLC.

Amgen has taken on one of the toughest challenges of the last 40 years in cancer research by developing sotorasib, the first KRASG12C inhibitor to enter the clinic.8 Sotorasib is being studied in the broadest clinical program exploring 10 combinations with global sites spanning across four continents. In just over two years, the sotorasib clinical trial program has also established the deepest clinical data set with nearly 700 patients studied across 13 tumor types.

About CodeBreaK
The CodeBreaK clinical development program for Amgen’s investigational drug sotorasib is designed to treat patients with an advanced solid tumor with the KRAS G12C mutation and address the longstanding unmet medical need for these cancers. As the most advanced KRAS G12C clinical development program, CodeBreaK has enrolled nearly 700 patients across 13 tumor types since its inception.

CodeBreaK 100, the Phase 1 and 2, first-in-human, open-label multicenter study, enrolled patients with KRAS G12C-mutant solid tumors. Eligible patients must have received a prior line of systemic anticancer therapy, consistent with their tumor type and stage of disease. The primary endpoint for the Phase 2 study was centrally assessed objective response rate. The Phase 2 trial in NSCLC enrolled 126 patients, 124 of whom had centrally evaluable lesions by RECIST at baseline. The Phase 2 trial in colorectal cancer is fully enrolled and topline results are expected in 2021.

A global Phase 3 randomized active-controlled study comparing sotorasib to docetaxel in patients with KRAS G12C-mutated NSCLC (CodeBreaK 200) is currently recruiting. Amgen also has more than 10 Phase 1b combination studies across various advanced solid tumors (CodeBreaK 101) open for enrollment.

For information, please visit www.codebreaktrials.com.