On September 7, 2022 GenFleet Therapeutics, a clinical-stage biotechnology company focusing on cutting-edge therapies in oncology and immunology, reported the results from phase I study of GFH018 (TGF-β R1 inhibitor) monotherapy (NCT05051241) for treatment of advanced solid tumor will be presented as a poster at the 2022 European Society for Medical Oncology Meeting in Paris on September 12th (Press release, GenFleet Therapeutics, SEP 7, 2022, View Source [SID1234619217]).

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Through an open-label, multicenter study, GFH018 demonstrated a favorable safety/tolerability profile and preliminary efficacy signal among advanced solid tumor patients that failed to respond to prior standard therapies. No dose-limiting toxicities were observed and over 20% patients with different types of cancer achieved stable disease. Two phase II combination studies of GFH018 with PD-1 inhibitor are ongoing with additional data to be presented at medical meetings in the future.

"We are delighted to collaborate with GenFleet in the clinical research of GFH018 as an innovative small-molecule kinase inhibitor designed to specifically target and inhibit TGF-β R1. We are pleased to report the preliminary efficacy signal and good safety/tolerability profile of GFH018 monotherapy and look forward to the further trials in combination studies." said Professor Ye Guo of Shanghai Oriental Hospital.

"It is the first time for GenFleet to present clinical data at ESMO (Free ESMO Whitepaper), which represents a significant milestone in the company’s multi-regional clinical research and global development. We have recently determined the recommended phase II dose and hope to confirm the response of combination therapies in patients with advanced tumors. Moreover, we expect to release more data related to GFH018 in future academic conferences." said Yu Wang, M.D./Ph.D., Chief Medical Officer of GenFleet.

Phase I study of GFH018, a small molecular TGF-β R1 inhibitor, in patients with advanced solid tumor

Poster 437p, Abstract：#1623, Poster Area: Hall 4

This is an open-label, multicenter study comprising of a modified 3 + 3 dose escalation part followed by an expansion part and the starting dose was 5 mg. Eligible patients with advanced solid tumors failed to standard therapies were administrated with GFH018 BID, 14d on/14d off in 28-day cycles. As of Jan. 25, 2022, 39 patients were sequentially enrolled in the dose escalation part. The median lines of prior therapy were≥3. No dose-limiting toxicities were observed, the maximum tolerated dose was not reached, and no patients discontinued the study treatment due to adverse events.

PK of GFH018 was linear and dose-independent with mean half-life in the range of 3.11 hours to 8.30 hours. Of 24 evaluable patients, 5 achieved stable disease. A patient with thymic carcinoma receiving 50 mg achieved a durable stable disease with tumor shrinkage (maximum lesion decreased by 18.4% and has stayed on treatment for 185 days as of the data cut-off date.

About GFH018 and TGF-β R1

Developed by GenFleet Therapeutics, GFH018 is an orally administered TGF-β R1 inhibitor and entered into phase I clinical trial in 2019. Preclinical data showed evidence of GFH018’s good anti-tumor properties against cancer cells in vivo and in vitro. Besides, translational and mechanistic studies confirmed it effectively acts on TGF-β signaling pathway and synergizes with checkpoint inhibitors.

In the microenvironment of advanced solid tumors, TGF-β signaling pathway can promote epithelial mesenchymal transition (EMT) & metastasis, induce the formation of cancer stem cells and their functional maintenance, inhibit anti-tumor immunity, enhance vasculature and fibrosis, and ultimately result in tumor progression. Among patients of hepatocellular carcinoma, glioma, colorectal cancer, lung cancer, pancreatic cancer, urothelial cancer and other solid tumors, high expression of genes related to TGF-β signaling pathway is frequently discovered in their blood and tumor tissues. The expression level is positively correlated to the malignancy & poor differentiation of tumor and unfavorable prognosis in patients.

On September 7, 2022 Cipla Limited (BSE: 500087) (NSE: CIPLA EQ) ("Cipla") reported that it has received final approval for its Abbreviated New Drug Application (ANDA) for Lenalidomide Capsule 5 mg, 10 mg, 15 mg and 25 mg from the United States Food and Drug Administration (US FDA) (Press release, Cipla, SEP 7, 2022, View Source [SID1234619216]).

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Cipla’s Lenalidomide Capsules are the AB-rated therapeutic equivalent generic version of Bristol Myers Squibb’s (Celgene) Revlimid (Lenalidomide) Capsules.

Lenalidomide is an immunomodulatory prescription drug which is indicated for several hematological malignancies in adults such as; Multiple Myeloma, Myelodysplastic syndromes, Mantle cell lymphoma, Follicular lymphoma, and Marginal Zone lymphoma. Depending on the type of cancer, it can be used as monotherapy or combination as a part of first line regimen, maintenance regimen or relapsed settings.

Lenalidomide capsules are not to be used by pregnant women. It is not known if lenalidomide is safe and effective for children. Lenalidomide Capsules should not be used to treat people with chronic lymphocytic leukemia (CLL) outside of a controlled clinical trial.

According to IQVIA (IMS Health), Revlimid (Lenalidomide) Capsules had US sales of approximately $ 2.58 billion for the 12-month period ending June 2022.

The product will be available for shipping soon.

On September 7, 2022 OncoResponse, a clinical-stage biotech company advancing immunotherapies derived from the immune systems of elite cancer responders, reported a clinical supply agreement with Regeneron for PD-1 inhibitor Libtayo (cemiplimab) (Press release, OncoResponse, SEP 7, 2022, View Source [SID1234619215]). The supply agreement will support the evaluation of Libtayo in combination with OR2805, a fully human monoclonal antibody identified from an elite cancer responder using OncoResponse’s proprietary B-cell discovery platform.

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"We believe the ability of OR2805 to potently activate myeloid cells within the tumor microenvironment will not only provide benefit as a monotherapy, but also improve responses to currently available checkpoint inhibitor immunotherapies such as Libtayo," said Bob Lechleider, MD, Chief Medical Officer of OncoResponse. "We look forward to evaluating the combination of OR2805 with Libtayo, which has demonstrated efficacy in pivotal trials, serving as the basis for FDA approval in three types of advanced cancers. We believe that this combination treatment approach has the potential to improve the outcomes of patients with cancer."

OR2805 is being evaluated in an ongoing Phase 1 study examining safety, pharmacokinetics and preliminary anti-cancer activity in patients with advanced solid tumors alone and in combination with anti-PD-1 therapy. The trial includes a dose escalation phase, followed by several expansion cohorts. The role of potential biomarkers will be evaluated throughout the study, and more intensively in a separate biology cohort. ClinicalTrials.gov identifier: NCT05094804

About OR2805

OR2805 is a fully human antibody discovered using B cells derived from an elite responder to checkpoint inhibitor (CPI) therapy. This antibody binds to CD163 which is highly expressed on tumor associated macrophages (TAMs) that create an immunosuppressive tumor microenvironment and inhibit anti-tumor T-cell responses. High frequency of CD163-expressing TAMs generally predicts an unfavorable prognosis in solid tumors. OR2805 is designed to improve anti-tumor T-cell responses, by reversing the immunosuppression of TAMs, as a therapeutic strategy for monotherapy and in combination with CPI.

On September 7, 2022 Citius Pharmaceuticals, Inc. ("Citius" or the "Company") ( Nasdaq: CTXR), reported that Citius will participate in the H.C. Wainwright 24th Annual Global Investment Conference being held September 12-14, 2022 (Press release, Citius Pharmaceuticals, SEP 7, 2022, https://www.prnewswire.com/news-releases/citius-pharmaceuticals-inc-to-present-at-the-hc-wainwright-24th-annual-global-investment-conference-301619139.html [SID1234619214]). Leonard Mazur, Chairman and CEO of Citius, will present in person on September 14, 2022 at 11:00am EDT, and host one-on-one meetings with investors.

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Registered participants will be able to view Mr. Mazur’s presentation live through the conference website or access an archived webcast of the presentation under "Events" in the Investors section of the Citius website. The archived webcast will be available for 90 days following the event.

On September 7, 2022 Lutris Pharma, a clinical stage biopharmaceutical company focused on improving anti-cancer therapies by reducing dose limiting side effects, reported positive top-line results from the open label part 1 and double blinded part 2 of its phase 1/2 trial of lead compound, LUT014, a topically applied, novel B-Raf inhibitor, for the treatment of radiation-induced dermatitis (RD) in patients with breast cancer (Press release, Lutris Pharma, SEP 7, 2022, View Source [SID1234619213]).

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Figure 1: Image of the irradiated area of a patient in part 1 of the study at baseline and at each visit (1 week intervals). Courtesy of Lutris Pharma.
Figure 1: Image of the irradiated area of a patient in part 1 of the study at baseline and at each visit (1 week intervals). Courtesy of Lutris Pharma.
Figure 2: Images of 2 patients in part 2 of the study after 1 week of treatment. On the left is a patient in the placebo arm. On the right is a patient treated with LUT014. Courtesy of Lutris Pharma.
Figure 2: Images of 2 patients in part 2 of the study after 1 week of treatment. On the left is a patient in the placebo arm. On the right is a patient treated with LUT014. Courtesy of Lutris Pharma.
Part 1 results showed that, of the eight patients who developed grade 2 RD at baseline, 75% (7/8) had complete resolution, improving to grade 0 dermatitis, and 100% of patients had RD of 1 or 0 as assessed by the Common Terminology Criteria for Adverse Events (CTAE) after 28 days of daily, topically applied LUT014 gel. All of the patients derived benefit in quality of life by day 28 as assessed by the validated, self-reporting Dermatology Life Quality Index (DLQI) questionnaire, with seven of eight patients experiencing no or small effect of the dermatitis on their respective quality of life after the treatment course. The primary endpoint of the open-label part 1 was the incidence of Treatment-Emergent Adverse Events as assessed by CTAE at 12 weeks and the data showed that LUT014 was generally well tolerated, no severe or serious adverse events occurred and no adverse events were associated with discontinuation of the study drug.

The primary endpoint of the double blinded part 2 of the phase 1/2 trial was the change in severity of radiation dermatitis, based on a validated self-reporting DLQI questionnaire at 14 days, as measured by improvement of at least 5 points on the DLQI at day 14. Of note, 8/8 (100%) of patients treated with LUT014 versus 8/11 (73%) of patients treated with placebo achieved the primary endpoint (27% absolute difference, Fisher’s Exact test, p=0.23). Secondary endpoints examined further quality of life variables as well as treatment effect. Improvement in the DLQI score at day 7 was noted by an increase of 30% in the treated arm versus placebo arm; the proportion of patients who showed improvement from grade 2 to grade 1 by day 7 was 75% (6/8) for patients who received LUT014 versus 54% (6/11) for patients who received placebo; and the proportion of patients who achieved complete recovery (grade 0) by day 28 was 50% (4/8) for LUT014 versus 36% (4/11) for placebo.

"We are extremely encouraged by the strong part 1 results and the equally impressive part 2 data, which show 100% of patients with radiation dermatitis in the LUT014 treatment arm experiencing a clinically meaningful treatment effect," stated Noa Shelach, Ph.D., Chief Executive Officer of Lutris Pharma. "The secondary endpoints reported were all supportive, as well, and further highlight the potential, unique ability of LUT014 to expedite patient recovery within just one to two weeks and to make a marked difference in quality of life. Given the fact that the majority of patients with breast cancer will develop radiation dermatitis, these results further empower our thesis about the promise of LUT014 to treat this patient population."

Benjamin W. Corn, M.D., Chief Medical Officer of Lutris Pharma, added, "Part 2 of the phase 1/2 study provided us with impactful information that supports the need for further study of LUT014 in this radiation-induced dermatitis indication. Based on the top-line results, the 100% success rate indicates that the active arm response is saturated and that there might be an even a greater effect that cannot be detected in the current study design. That said, we believe we may be able to see a higher effect between treatment and placebo arms if LUT014 is started earlier, right after a patient’s radiation treatment."

Antoni Ribas, M.D., Chairman of the Board of Directors of Lutris Pharma, noted, "These favorable results in patients with radiation dermatitis, coupled with the highly encouraging data generated, thus far, in the company’s study of LUT014 in patients with mCRC with EGFR inhibitor induced acneiform lesions, tells us that the LUT014 compound is active to treat skin conditions that could benefit from the topical administration of this small molecule BRAF inhibitor, which opens the door to its use in numerous additional indications, and we look forward to exploring these options and expanding the pipeline in the future."

For more information about this clinical trial, please visit: www.clinicaltrials.gov, NCT04261387.

About LUT014

LUT014 is a novel B-Raf inhibitor which is applied topically on the skin. When the B-Raf protein is mutated, as is the case in some human cancers such as melanoma cancer, blocking this pathway leads to apoptosis of the cells and tumor shrinkage. However, when the same pathway is blocked in normal, non-mutated cells, the opposite happens: the MAPK pathway is activated, and cells start growing. This phenomenon is recognized as the paradoxical effect of B-Raf Inhibitors. LUT014 harnesses the paradoxical effect of B-Raf Inhibitors in order to enhance cell proliferation and balance cell destruction, typical to radiation dermatitis.

About Radiation Dermatitis

Radiation therapy results in ionization events that lead to damage of cellular macromolecules, including double-stranded DNA breaks. Within the epidermis, this DNA damage disrupts the normal proliferation and differentiation of basal keratinocytes, depleting the differentiated epidermal keratinocytes and ultimately resulting in the loss of the protective barrier provided by the skin. This, combined with DNA damage disruption within the dermis, which results in a complex sequence of effects including an immune response cascade, leads to the symptomology associated with radiation dermatitis, which can dramatically diminish a patient’s quality of life.

There is currently no FDA-approved drug whose labelled indication is for the prevention or treatment of radiation-induced dermatitis. Rather, patients are merely treated with supportive cutaneous care. These treatments – which have a weak evidence base — have included topical steroids, non-steroidal anti-inflammatory topicals, and hyaluronic acid derivatives. To date, none has been definitively proved efficacious.