On September 16, 2021 TAE Life Sciences (TLS), a biological-targeting radiation therapy company developing next-generation boron neutron capture therapy (BNCT), reported a partnership with BEC GmbH (BEC) to incorporate a customized, robotic patient positioning system as part of its Alphabeam Neutron System for the high-precision radiation treatment of tumors (Press release, TAE Life Sciences, SEP 16, 2021, View Source [SID1234587841]).

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During BNCT, it is essential that the patient is positioned accurately in relation to the radiation beam and that the radiation therapist has the ability to adjust the patient’s position throughout the whole treatment session. BEC will be developing a unique chair setup that will allow for flexible patient treatment in a seated position in addition to the traditional treatment couch configuration. Exclusively designed for TLS’ Alphabeam Neutron System, the chair is optimal for treating specific types of head and neck cancers.

"The exact positioning of the patient and the ability to adjust as necessary during treatment is paramount in BNCT and we are thrilled to partner with BEC to adopt the best positioning system available today," said Bruce Bauer, PhD, CEO of TAE Life Sciences. "BEC is renowned in its field and the coupling of our BNCT therapy with its positioning system provides the best of both worlds in helping to treat invasive, recurrent and difficult to treat cancers."

Installed in the ceiling and equipped with a linear axis, BEC’s exacure system positions patients for treatment in front of the radiation beam in a stable and flexible manner, while allowing for up to 7 levels of movement. The camera system monitors the position of the patient treatment table 500 times per second and applies corrections in real time, if necessary, to ensure optimal treatment results. The requirements for medical devices that are used for BNCT treatment differ substantially from the requirements for systems used in conventional radiotherapy, as material properties become degraded by neutron irradiation. BEC provides the first certified complete system that guarantees safe operation of all components even under the effects of neutron radiation.

"Our robotic patient positioning system was developed specifically for partners like TAE Life Sciences that have created next-generation BNCT as a first line treatment for cancer patients, and we look forward to working together to provide flexible robotic patient positioning for high-end radiation treatment," said Matthias Buck, CEO of BEC GmbH.

On September 16, 2021 Laekna Therapeutics, an emerging innovative biotech company based in China’s "Zhangjiang Pharma Valley" and New Jersey, USA, focusing on the development of ground-breaking innovative therapies to treat cancer and liver diseases, reported positive results in two clinical studies for the treatment of early and late stages of prostate cancer respectively at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress 2021 today (Press release, Laekna Therapeutics, SEP 16, 2021, View Source [SID1234587856]).

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The first study with LAE001 monotherapy targeting early stage of prostate cancer, and the second study with combination therapy of LAE001 + afuresertib in drug-resistant late stage prostate cancer, demonstrated positive and encouraging results by Laekna Therapeutics.

E-Poster: 597P

A Phase I Dose-Escalation Study of LAE001 In Patients with Metastatic Castration-Resistant Prostate Cancer (mCRPC)

Lead author and presenter: Dr. Dingwei Ye (Shanghai, China)

This ClinicalTrials NCT03843918 is a phase I dose-escalation and expansion study of LAE001 monotherapy without steroid, in patients with metastatic castration-resistant prostate cancer (mCRPC). LAE001 is the first CYP17A1/CYP11B2 dual inhibitor globally.

Results:

As of May 25, 2021, 27 pts (16, 5, 3, 3 pts in the 50, 75, 100 and 125 mg BID cohorts, respectively) enrolled in the phase Ia & Ib part and had a median 7.3 months follow up (1-25 months). Based on safety data, 50mg BID of LAE001 was selected as the RP2D; no DLT nor AE leading to discontinuation was reported under the RP2D, and the related serious adverse event (SAE) in the RP2D cohort was 6%.

Out of 15 patients treated in 50mg bid cohort, 11 pts (73%) had a >50% best PSA decline from baseline, among whom 6 pts (40%) had >90% PSA decline from baseline.
2 pts (50mg bid) had a PSA response that sustained for >52 weeks; 81% patients are ongoing treatment at the cut-off date.
Conclusions:

LAE001 monotherapy without steroid co-use is safe and well-tolerated at 50mg BID level (RP2D). The preliminary antitumor activity of LAE001 monotherapy at RP2D level supports the potential clinical benefit of treating patients with mCRPC. Further expansion phase 1b and II[1] study at RP2D is ongoing.

E-Poster: 599P

A Phase I Dose-Escalation Study of LAE001/Prednisone Plus Afuresertib in Patients with Metastatic Castration-Resistant Prostate Cancer (mCRPC) Following Standard of Care (SOC) Treatment

Lead author and presenter: Dr. Alberto Bessudo (Encinitas, CA, United States of America)

This ClinicalTrials NCT04060394 is a phase I dose-escalation study of a combination therapy with LAE001/prednisone plus afuresertib in patients with metastatic castration-resistant prostate cancer (mCRPC) following failed average 3,3 lines of prior SOC treatments. Afuresertib (LAE002) is an oral, small molecule pan-AKT kinase inhibitor. Whereas LAE001 is the first CYP17/CYP11B2 dual inhibitor globally.

Results:

As of 06/29/2021, 14 pts (8 in cohort 1 and 6 in cohort 2) received study treatment with median 12.5 months follow up. The dose of LAE001 75 mg BID/prednisone 5 mg BID and afuresertib 125 mg QD was determined as the RP2D. 2 DLTs were reported in cohort 1 (thrombocytopenia) and cohort 2 (skin rash), respectively, and only one non-DLT grade >= 3 treatment-emergent adverse events (TEAE) (skin rash) in cohort 2 (RP2D).

2 pts had a PSA response (2/10, 20%). Among 5 pts who have measurable lesions, 1 PR and 2 SDs were reported.
The 10 evaluable pts on average had failed 3.3 lines of SOC.
Conclusions:

The combination therapy of LAE001 75mg BID/prednisone 5mg BID and afuresertib 125mg QD was determined as the RP2D. The preliminary antitumor activity under the RP2D supports the potential clinical benefit for treating drug-resistant mCRPC and moves forward this study to phase II stage.

Encouraging results for patients with prostate cancer to soon benefit from LAE001 and afuresertib

"As an emerging innovative biotech company, Laekna Therapeutics is proud to make its debut at the ESMO (Free ESMO Whitepaper) Congress. We are very pleased to present the results from two clinical studies at this influential academic conference," said Dr Yue Yong, Chief Medical Officer of Laekna Therapeutics.

Prostate cancer is the most common cancer occurring in men world-wide. The monotherapy trial of LAE001 showed that the drug can be used without prednisone, and still demonstrate a tolerable safety profile and strong anticancer efficacy. Laekna plans to further develop LAE001 for patients with mHSPC who require a much longer treatment duration, and would benefit more from the ability to use LAE001 without prednisone.

Currently there is limited treatment options for NAAR drug-resistant mCRPC patients. The combination therapy of LAE001 and afuresertib is intended to benefit patients with PTEN/PIK3CA/AKT alterations.

"The topline data reported by Laekna Therapeutics at the ESMO (Free ESMO Whitepaper) Congress, a top international academic conference marks significant progress for Laekna’s clinical programs," Dr Yue Yong remarked. "With the continued advancement of the above two studies, we have seen more encouraging results in the enrolled patients in the past three months. We hope patients with both early- and late-stage prostate cancer can soon benefit from these two new innovative medicines."

[1] Patient enrollment of the Phase II trial is expected to start between the fourth quarter of 2021 and the first quarter of 2022

About European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress 2021

The ESMO (Free ESMO Whitepaper) Congress is one of the most influential oncology forums, where participants present the latest advances in the treatment of cancer and have cross-discipline exchanges and discussions. In response to the COVID-19 pandemic, the congress will be held virtually September 16-21, 2021.

About CYP17A1/CYP11B2 dual inhibitor (LAE001)

LAE001 is the first CYP17/CYP11B2 dual inhibitor globally. It is a novel, potent, non-steroidal, reversible dual inhibitor of CYP17 and CYP11B2 (aldosterone synthase) that blocks both androgen and aldosterone synthesis. It will be used as a treatment option for metastatic prostate cancer.

Compared to Abiraterone acetate, a CYP17 enzyme inhibitor that causes hyperaldosteronism, which requires long-term use of corticosteroids and may cause serious side effects, LAE001 has demonstrated similar therapeutic efficacy and improved safety profile in patients with drug-resistant mCRPC. Due to its dual inhibition of both CYP17 and CYP11B2, two critical enzymes for testosterone and aldosterone synthesis, LAE001 does not increase aldosterone level, therefore reduces the risk of cardiovascular toxicity and hepatotoxicity related to long-term prednisone use.

About Afuresertib (LAE002)

Afuresertib (LAE002) is a differentiated oral, small molecule pan-AKT kinase inhibitor that has been investigated in over 10 Phase 1/2 clinical trials, including ovarian cancer, gastric cancer, multiple myeloma, and melanoma. These studies have demonstrated that afuresertib has strong anti-cancer activities and a tolerable safety profile. The global randomized, open-label, multi-center Phase 2 PROFECTA-II clinical trial of afuresertib is the world’s first registration-directed clinical study of a pan-AKT kinase inhibitor to treat platinum-resistant ovarian cancer.

In recent years, AKT (a serine/threonine-protein kinase) has emerged as an important mechanism in oncology, as it plays an important role in regulating various cell functions such as metabolism, survival, proliferation, tissue invasion, and chemotherapy resistance. PTEN deletion and AKT/PIK3CA alteration may lead to excessive activation of the AKT signaling pathways, which is one of the key drivers for cancer growth. The increased activation of the AKT signaling pathway is particularly common in recurrent ovarian cancer, breast cancer, and prostate cancer.

On September 16, 2021 Biomea Fusion, Inc. ("Biomea") (Nasdaq: BMEA), a biopharmaceutical company focused on the discovery and development of irreversible small molecules to treat patients with genetically defined cancers, reported that the U.S. Food and Drug Administration (FDA) has cleared the company’s Investigational New Drug application to begin a Phase I trial of BMF-219, a selective irreversible menin inhibitor, in adult patients with relapsed or refractory acute leukemia including those with an MLL/KM2TA gene rearrangement or NPM1 mutation (Press release, Biomea Fusion, SEP 16, 2021, View Source [SID1234587873]).

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"First of all, I would like to take this opportunity to thank the FDA, the Contract Research Organizations, our consultants, our investors, and of course TEAM FUSION for the commitment, guidance, support, and tireless effort in getting BMF-219, an investigational new drug, in the hands of patients in need. It was a true community effort, and we are so blessed here at Biomea to be in position to provide an impactful therapy against aggressive cancers," said Thomas Butler, Biomea’s CEO and Chairman of the Board. "This is just the beginning for BMF-219 as we are planning to pursue multiple indications with our novel molecule. This is also just the beginning for the company, as we continue to make significant progress with our pipeline programs. We are in a strong position to continue to bring novel small molecules into the clinic and help the many patients with life threatening and life altering diseases."

"Over the past 6 months, we have brought together a first-class team of biotech professionals to tackle our next phase of growth, which will include clinical development of BMF-219 in not only liquid but also solid tumors," said Ramses Erdtmann, Biomea’s COO and President. "BMF-219 is a very special compound, with a unique effect on menin which we believe will lead to improved outcomes for patients with specific gene arrangement and mutations."

An irreversible small molecule, such as BMF-219, is a synthetic compound that forms a permanent bond to its target protein and offers a number of potential advantages over conventional reversible drugs, including greater target selectivity, lower drug exposure, and the ability to drive a deeper, more durable response.

The Phase 1, first-in-human, open-label, dose-escalation and dose-expansion clinical trial of BMF-219 will assess the safety, pharmacokinetic (PK) and pharmacodynamic (PD) profile of BMF-219 in adult patients with relapsed or refractory acute leukemia including those with an MLL/KM2TA gene rearrangement or NPM1 mutation.

About Acute Myeloid Leukemia (AML)

AML is the most common form of acute leukemia in adults and represents the largest number of annual leukemia deaths in the U.S. and Europe. AML originates within the white blood cells in the bone marrow and can rapidly move to the blood and other parts of the body, including the lymph nodes, spleen, and central nervous system. Approximately 30,000 people in the U.S. and Europe are diagnosed with AML each year, and the five-year overall survival rate in adults roughly 29%. Among patients with relapsed/refractory disease, the need is greatest, as the overall survival is approximately 3 to 9 months. It is estimated that upwards of 45% of AML patients have menin dependent genetic drivers (MML-r or NPM1).

About BMF-219

BMF-219 is an irreversibly binding inhibitor of menin, a protein that is known to play an essential role in oncogenic signaling in genetically defined leukemias. Preclinically, BMF-219 has demonstrated robust downregulation of key leukemogenic genes in addition to menin itself (via MEN1) in well-established MLLr AML cell lines. Additionally, BMF-219 has shown efficacy in multiple in vivo and in vitro models of acute leukemias. BMF-219 will be evaluated in a first-in-human trial in patients with relapsed or refractory acute leukemia with MLL/KM2TA gene rearrangement or NPM1 mutation.

On September 16, 2021 Carrick Therapeutics, an oncology-focused biopharmaceutical company discovering and developing highly differentiated therapies, reported that encouraging initial clinical data on samuraciclib (CT-7001), an oral and first-in-class inhibitor of CDK7, at the 2021 European Society of Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress (Press release, Carrick Therapeutics, SEP 16, 2021, View Source [SID1234587940]).

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Data presented from a Phase 2a study of samuraciclib in combination with fulvestrant in women with hormone receptor positive (HR+), HER2- advanced breast cancer (BC) previously treated with a CDK4/6 inhibitor (abstract: 1346 (265P)) demonstrated clinical activity and tolerability that supports further clinical development of the combination.

"Today, for the first time, we presented data from a clinical trial of our oral CDK7 inhibitor, samuraciclib. Results of the Phase 2a study in combination with fulvestrant demonstrated clinical activity and tolerability in patients with HR+, HER2- advanced breast cancer, reinforcing our conviction that samuraciclib has potential to be a first and best-in-class treatment," said Tim Pearson, Chief Executive Officer of Carrick Therapeutics. "As a reminder, the FDA recently granted Fast Track designation to samuraciclib in combination with fulvestrant for CDK4/6 inhibitor resistant patients. This patient population is particularly difficult to treat, with a recent trial showing only 8 weeks mPFS benefit when women are treated with fulvestrant alone. Based on this initial data, we believe samuraciclib has the potential to provide a clinically meaningful benefit for all patients, most notably in those women that are TP53 wildtype. In addition to fulvestrant, we are exploring additional samuraciclib combinations, including with giredestrant, a next-generation oral SERD, through our recently announced clinical collaboration with Roche in metastatic breast cancer. We thank the women that participated in this Phase 2a trial and look forward to continuing the fight against this and other types of cancer."

As part of the Phase 2a study of samuraciclib in combination with fulvestrant in patients with advanced HR+, HER2- BC, 31 patients were enrolled with difficult-to-treat disease. 81% of these patients had visceral disease, including 45% with liver metastasis. All patients enrolled previously progressed following treatment with a CDK4/6 inhibitor. Of the 31 patients enrolled in the study, 24 patients were evaluable for response at the time of data cut-off:

17 (71%) had tumour shrinkage, with a best RECIST response of partial response (PR) in two (8%) patients and stable disease (SD) in 13 (54%) patients.
Median progression-free survival (mPFS) of the intent-to-treat (ITT) population was 16.1 weeks (n=31).
Notably, patients with no mutation in the TP53 gene had a mPFS of 32.0 weeks (n=18).
Prolonged disease control was also apparent in patients with no liver metastases at baseline (n=17), with mPFS having not yet been reached. At the point of this data cut-off, mPFS would be at least 28 weeks.
Adverse events were predominantly low-grade gastrointestinal (GI) events that were reversible and manageable using standard prophylactic treatment. No significant neutropenia or myelosuppression associated with other CDK inhibitors were observed.
This data supports the further development of samuraciclib in HR+ advanced BC.
"The data from this study show excellent preliminary evidence of activity of samuraciclib in combination with fulvestrant," said Dr. Sacha Howell, The Christie NHS Foundation Trust, Manchester, UK and a primary investigator in the Phase 2a study. "This population of patients, previously treated with CDK4/6 inhibitors, are known to have previously demonstrated short PFS benefit from fulvestrant alone. The efficacy data, particularly in participants with wildtype TP53, exceeded my expectations and offers the potential for durable endocrine disease control, further delaying the need for chemotherapy. Those participants remained on therapy for prolonged durations demonstrates tolerability and the main GI toxicity was manageable with supportive medication."

"Following the positive initial Phase 2a data, we are preparing to advance the randomized Phase 2b study of HR+, HER2-, post-CDK4/6 inhibitor breast cancer patients," said Dr. Stuart McIntosh, Chief Medical Officer of Carrick Therapeutics. "A key distinction from the Phase 2a will be the inclusion of patients with RECIST non-measurable disease in addition to those with visceral disease in the Phase 2b, in-line with the real-world population. Given the success noticed in the sub-group of patients with no mutation in the TP53 gene population, we will prospectively evaluate and stratify by mutation status as well. This success aligns with the known biological function of TP53 since its activation has been shown to sensitize cancer cells to CDK7 inhibition. Approximately 75% of breast cancer patients are TP53 wild-type, and we believe this may be an important potential biomarker for future studies."

In addition to the Phase 2a data presented today, data from the first-in-human study of samuraciclib in patients with advanced solid malignancies (abstract: 943 (230MO)) will be shared during an oral presentation at ESMO (Free ESMO Whitepaper) from 17:10 BST (12:10pm ET) on September 18, 2021. As part of the study, 44 patients were treated with escalating doses of samuraciclib monotherapy, which demonstrated evidence of antitumor activity with a manageable safety profile.

About Samuraciclib (CT7001)
Samuraciclib is the most advanced oral CDK7 inhibitor in clinical development. Inhibiting CDK7 is a promising therapeutic strategy in cancer as CDK7 regulates the transcription of cancer-causing genes, promotes uncontrolled cell cycle progression and resistance to anti-hormone therapy. Samuraciclib has demonstrated a favorable safety profile and encouraging efficacy in early clinical studies. In addition to the above study, it is currently being evaluated in triple negative breast cancer (TNBC) and prostate cancer with further potential in pancreatic, ovarian and colorectal cancers. Samuraciclib has been granted Fast Track designations from the U.S. Food and Drug Administration (FDA) for use in combination with fulvestrant for the treatment of CDK4/6i resistant HR+, HER2- advanced breast cancer and in combination with chemotherapy for the treatment of locally advanced or metastatic TNBC.

On September 16, 2021 Monopar Therapeutics Inc. (Nasdaq: MNPR), a clinical-stage biopharmaceutical company focused on developing proprietary therapeutics designed to extend life or improve the quality of life for cancer patients, reported its Phase 1b open-label dose-escalation clinical trial of camsirubicin in the US is active and recruiting patients (Press release, Monopar Therapeutics, SEP 16, 2021, View Source [SID1234587824]). The trial is evaluating the safety and anti-tumor activity of increasing doses of camsirubicin in combination with growth factor support (pegfilgrastim/G-CSF) for the treatment of advanced soft tissue sarcoma (ASTS).

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"This trial initiation marks a pivotal moment in the development of camsirubicin. The goal is to determine whether escalating doses of camsirubicin result in an increased anti-cancer effect in patients with ASTS, while also maintaining an appropriate safety profile," said Chandler Robinson, MD, Monopar’s Chief Executive Officer.

"We are very pleased with the positive response and dedication from physicians and clinical sites interested in participating in this clinical trial, enabling us to initiate the study in the US faster than we anticipated," said Octavio Costa, MD, Monopar’s Chief Medical Officer.

Currently, ASTS patients receive doxorubicin, a widely used cancer drug that becomes more effective in higher doses. Unfortunately, patients are forced to stop treatment once a cumulative lifetime dose limit is reached, as higher dosing causes severe irreversible heart damage.

"Camsirubicin has already shown anti-tumor activity comparable to doxorubicin in a pilot study in ASTS patients, without any signs of irreversible heart damage," said Andrew Mazar, PhD, Monopar’s Chief Scientific Officer. "We are excited, as the previous study’s dose of camsirubicin will be the first dose level in this Phase 1b clinical trial. From there the dose will increase, hopefully with corresponding increases in anti-cancer effect, to identify a recommended Phase 2 dose (RP2D) of camsirubicin when given with concomitant pegfilgrastim."

Further information about the camsirubicin trial is available at www.ClinicalTrials.gov under study identifier NCT 05043649.

About Camsirubicin

Camsirubicin is a novel proprietary analog of the widely used cancer drug doxorubicin. It has been investigated in ASTS patients in a Phase 1 and a single arm Phase 2 clinical trial. In these studies, no camsirubicin-treated patients developed the irreversible cardiotoxicity common to doxorubicin at higher cumulative doses. The most frequent adverse event observed in the Phase 1 study was neutropenia, which was mitigated in the Phase 2 study through the use of prophylactic G-CSF. Based on encouraging clinical results to date, the Phase 1b trial is designed to test camsirubicin at even higher doses than previously administered while using concomitant prophylactic G-CSF to prevent neutropenia.

About Soft Tissue Sarcoma

Soft tissue sarcomas (STS) are a diverse type of cancer that typically develop in the connective tissue of the body. According to the American Cancer Society, in 2021, an estimated 13,460 new STS cases will be diagnosed in the US alone, and about 5,350 people will not survive their disease. These tend to be the advanced cases; those with sarcomas that are unresectable and/or have metastasized. The average life expectancy from time of diagnosis for those patients with advanced disease (ASTS) is about 12 to 15 months. Doxorubicin is the current standard of care in the 1st-line setting for ASTS, and has been for decades, since there have been no 1st-line therapeutic advancements that have improved overall survival for this patient population.