On February 14, 2022 Taiho Pharmaceutical Co., Ltd. reported that it has submitted to the Japanese Ministry of Health, Labour and Welfare, an application for the additional indication of "postoperative adjuvant chemotherapy in breast cancer" for its oral anticancer agent TS-1 (Press release, Taiho, FEB 14, 2022, View Source [SID1234608061]).

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This application is based on the results of an investigator-initiated study, Postoperative Therapy with TS-1 for oestrogen receptor-positive, HER2-negative breast cancer (POTENT study). According to the results of the POTENT study, the combination of TS-1 with endocrine therapy showed a clinically significant extension of invasive disease-free survival (iDFS) among patients with oestrogen receptor-positive, HER2-negative breast cancer with an intermediate or higher risk of recurrence. The safety profile was similar to that of TS-1 reported in the past, and no new concerns were identified in the POTENT study.

Taiho Pharmaceutical will continue to prepare for the delivery of this treatment option to patients with breast cancer, aiming to obtain approval as quickly as possible.

About the POTENT Study
POTENT is an investigator-initiated study conducted since March 25, 2011, under the designation of advanced medical care (Specific Clinical Research jRCTs051180057，UMIN000003969). The principal investigator, Masakazu Toi, M.D., Ph.D., Professor of Breast Surgery at Kyoto University’s Graduate School of Medicine and Faculty of Medicine, had submitted a study application to the Japanese Ministry of Health, Labour and Welfare under the former Advanced Medical Care Program. On January 25, 2011, the Advanced Medical Care Assessment Council approved the study with the advanced medical care name, "Postoperative Therapy with TS-1 for oestrogen receptor-positive, HER2-negative breast cancer."

The purpose of the study was to verify any increase in the effect on prevention of recurrence through a randomized comparative Phase III study in postoperative adjuvant therapy for oestrogen receptor-positive, HER2-negative breast cancer. The control group was treated with endocrine therapy (5 years), the standard treatment method, with the study group treated with endocrine therapy (5 years) in combination with TS-1 (1 year). The study endpoints included invasive disease-free survival, overall survival, safety, etc. The study enrolled 1,959 women from 139 breast cancer facilities across Japan during the registration period from February 2012 to February 2016.1

Public Health Research Center, contracted to serve as the study management office, received funding from Taiho Pharmaceutical and this study was conducted with such funding.
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1 Toi M et al., Lancet Oncol 2021; 22: 74–84.

For more information of the POTENT study, please refer to
View Source
View Source (in Japanese only)

About Primary Breast Cancer
According to the Japan Breast Cancer Society’s Annual Report of the Japanese Breast Cancer Registry for 2017,2 94,612 women in Japan are affected by breast cancer annually. It is reported that 75.3% of these cases are oestrogen receptor-positive, HER2-negative breast cancer. In cases of early-stage breast cancer, perioperative chemotherapy and postoperative endocrine therapy are given as standard treatments in addition to surgery, considering the risk of recurrence.

2 Hayashi N et al., Breast Cancer 2020; 27:803–809.

About TS-1
A member of the fluoropyrimidine class of anticancer agents, TS-1 is a combination of three pharmacological compounds: tegafur, an antimetabolite agent that, after absorption, is converted into the anticancer agent fluorouracil (5-FU); gimeracil (5-chloro-2, 4-dihydroxypyridine, or CDHP), which decreases the degradation of 5-FU in the liver; and oteracil (Oxo), which decreases 5-FU phosphorylation in the gastrointestinal tract. Developed as a gastric cancer treatment, TS-1 was first approved in Japan in 1999 and has become a standard of care for the treatment of gastric cancer. TS-1 has been approved in Japan for the treatment of gastric, colorectal, head and neck, non-small cell lung, inoperable or recurrent breast, pancreatic, and biliary tract cancers.

On February 14, 2022 Biodesix, Inc. (NASDAQ: BDSX) a leading data-driven diagnostic solutions company with a focus in lung disease, reported that the Company expects to report fourth quarter and record full-year 2021 preliminary unaudited total revenue of $7.2 million and $54.5 million, respectively (Press release, Biodesix, FEB 14, 2022, View Source [SID1234608060]). The strength in the full-year 2021 total revenue of $54.5 million compared to $45.6 million in 2020 was a result of growth in the Company’s core lung diagnostic testing and first half 2021 COVID-19 testing. The financial results included in this release pertaining to the fourth quarter and year ended December 31, 2021 are preliminary and unaudited and subject to final review and adjustments.

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Fourth Quarter and Full-Year 2021 Financial Highlights

•Total quarterly revenue of $6.8 million, excluding COVID-19 testing revenue, increased $1.2 million or 22% for the fourth quarter 2021 compared to the same period in 2020 and $0.8 million or 13% for the fourth quarter 2021 compared to the third quarter 2021; and
•Total annual revenue of $24.3 million, excluding COVID-19 testing revenue, increased $7.1 million or 41% for the year ended December 31, 2021 compared to the same period in 2020.
•Cash and cash equivalents as of December 31, 2021 of $32.7 million.
"We are pleased to see the continued growth in our core lung diagnostic business throughout 2021 despite the challenges created by the ongoing pandemic," stated Scott Hutton, Chief Executive Officer. "With the launch of our new IQLung Treatment Guidance Testing Strategy, which includes the new GeneStrat NGS test and provides for both early and advanced stage lung cancer testing results, our Nodify Lung testing for lung nodule risk assessment, as well as the broad array of tests that we perform on behalf of our biopharmaceutical partners, we are very well positioned to continue to drive growth in our core business in 2022. As we said in our third quarter earnings call, given our current financial position, including covenants under our current debt facility, we will continue to explore paths to greater liquidity, including raising capital through additional equity and/or debt as the markets continue to evolve, and through partnering opportunities."

On February 14, 2022 Moleculin Biotech, Inc., (Nasdaq: MBRX) ("Moleculin" or the "Company"), a clinical stage pharmaceutical company with a broad portfolio of drug candidates targeting highly resistant tumors and viruses, reported preliminary results supporting the successful conclusion of its second Phase 1 trial (MB-105) in Poland evaluating Annamycin for the treatment of relapsed and refractory acute myeloid leukemia (AML), where Moleculin determined a dose of 240 mg/m2 as the Recommended Phase 2 Dose (RP2D), subject to final approval of the Safety Review Committee, and indicated no signs of cardiotoxicity (a common problem with currently prescribed anthracyclines) (Press release, Moleculin, FEB 14, 2022, View Source [SID1234608059]). Based on preclinical animal data from sponsored research conducted simultaneous with its clinical trials, Annamycin in combination with Cytarabine demonstrated a 68% improvement in the median overall survival (OS) compared to Annamycin as a single agent and a 241% increase in OS compared to Cytarabine alone. Based on this data, the Company plans to advance its AML clinical development program in a Phase 1/2 clinical trial in Europe evaluating the combination of Annamycin and Cytarabine utilizing the clinical data from its two prior Phase 1 clinical trials.

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"This important study conclusion now allows us to combine the safety and efficacy data from our MB-104 and MB-105 AML clinical trials using Annamycin as a single agent, along with the recent findings from preclinical studies showing that the combination of Annamycin with Cytarabine (AnnAraC) has the ability to synergistically improve activity against AML and move directly into a new AML clinical trial to study AnnAraC in humans," Dr. J. Paul Waymack, Senior Chief Medical Officer of the Company, commented. He continued, "The support of local physicians in Poland for an AML trial utilizing AnnAraC is encouraging, and we believe this will translate into a faster pace of recruitment than we experienced in our MB-105 clinical trial. As such, our Annamycin AML program is now positioned to progress to a Phase 1/2 combination clinical trial in Europe as soon as possible. We expect to begin this trial in the first half of this year."

"The RP2D will assist in setting the initial dosage in the AnnAraC clinical trial but imposes no limit on Annamycin as the new clinical study will have its own Phase 1 dose escalation portion setting a new RP2D for the combination. The successful outcome of our second Phase 1 study combined with the data we have seen to-date represents a major milestone in the AML program as we believe successful Phase 2 data from the combination trial could position AnnAraC for late-stage development and faster approval in AML versus Annamycin as a single agent," added Mr. Walter Klemp, Chairman and CEO of Moleculin Biotech.

In January, the Company reported that it had received an updated independent safety review of certain preliminary data for the first 30 patients in its three Phase 1 clinical trials with Annamycin targeting AML (MB-104 and MB-105) and the metastases of soft tissue sarcoma to the lungs (STS Lung) or MB-107, which concluded there was no evidence of cardiotoxicity. Specifically, the trial Moleculin is concluding (MB-105), began its first cohort with an initial dose of 120 mg/m2 for three consecutive days. Each cohort contained three patients receiving a full course of Annamycin. In the fifth and final cohort, patients’ daily dose was 240 mg/m2 with five patients receiving a full course of Annamycin. The overall response rate (ORR) was 60% in the last cohort. This included two partial responses (PR’s) and one complete response with incomplete recovery of neutrophils and/or platelets (CRi). Upon safely reaching the RP2D of 240 mg/m2 in the MB-105 trial, the Company has concluded recruitment for the trial. The data from MB-104 and MB-105 trials will be used to design and support the new proposed combination trial.

The clinical data presented above are preliminary and subject to changes as the final clinical study report will be prepared in the near term.

The Company reported in November of 2020 new animal data from its sponsored research program showing highly improved activity against acute myeloid leukemia when Annamycin was used in combination with the commonly used antileukemic drug Cytarabine (Ara-C) versus single agent. The data was presented at the 62nd Annual Meeting & Exposition of the American Society for Hematology ("ASH") under the title: "High Efficacy of Liposomal Annamycin (L-ANN or Annamycin) in Combination with Cytarabine in Syngeneic p53-null AML Mouse Model."1 This study demonstrated vastly higher efficacy of the L-ANN/ARA-C combination (AnnAraC) over that of the single agents in an immune-competent setting of an aggressive, p53-null AML model. The study summarily demonstrated a 68% improvement in median OS of the animals in the study compared to Annamycin as a single agent and a 241% increase in OS compared to Cytarabine alone.

1 Zal T, Zielinski R, Grela K, Cardenas-Zuniga R, Skora S, Fokt I, Zal A, Andreeff M, Gil L Shephard R, Priebe W, High Efficacy of Liposomal Annamycin (L-ANN) in Combination with Cytarabine in Syngeneic p53-Null AML Mouse Model, Blood (2020) 136 (Supplement 1): 6–7. View Source

About Annamycin

Annamycin is the Company’s next-generation anthracycline that has been shown in animal models to accumulate in the lungs at up to 30-fold the level of doxorubicin. Importantly, Annamycin has also demonstrated a lack of cardiotoxicity in multiple human clinical trials, including ongoing trials for the treatment of relapsed or refractory acute myeloid leukemia (AML) and soft tissue sarcoma (STS) lung metastases, and the Company believes that the use of Annamycin may not face the same usage limitations imposed on doxorubicin, one of the most common currently prescribed anthracyclines. Annamycin is currently in development for the treatment of AML and STS lung metastases and the Company believes it may have the potential to treat a number of additional indications.

Annamycin currently has Fast Track Status and Orphan Drug Designation from the U.S. Food and Drug Administration for the treatment of STS lung metastases, in addition to Orphan Drug Designation for the treatment of relapsed or refractory acute myeloid leukemia. For more information about the Phase 1b/2 study evaluating Annamycin for the treatment of STS lung metastases, please visit clinicaltrials.gov and reference identifier NCT04887298.

On February 14, 2022 Primmune Therapeutics, a biotech company harnessing the power of the innate immune system to treat cancers and viral diseases, reported that interim data related to PRTX007, a novel, orally administered, small molecule toll-like receptor 7 (TLR7) specific agonist that is currently in Phase 1 development, at the Conference on Retroviruses and Opportunistic Infections (CROI) (Press release, Primmune Therapeutics, FEB 14, 2022, View Source [SID1234608058]). Oral administration of PRTX007 in this first-in-human study of healthy volunteers exhibited a favorable safety profile, rapid absorption and conversion to TLR7 agonist PRX034, and activation of the innate immune system, without causing inflammation.

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"PRTX007 is being developed to harness the power of the innate immune system by targeting TLR7, without increasing cytokines that can result in hyperinflammation and can harm patients," said James Appleman, Ph.D., Co-Founder and Chief Scientific Officer at Primmune Therapeutics. "We look forward to continuing the development of PRTX007 to address current unmet needs of patients with cancers and viral infections."

Highlights of this data, presented in a poster titled "Interim Analysis of a Phase 1 Study of PRTX007: Safety, PK, and PD Response," include:

Oral administration of PRTX007 resulted in efficient systemic delivery and well-behaved pharmacokinetics of agonist PRX034
TLR7-mediated immune response was shown to be dose and exposure-dependent
TLR7-mediated immune induction of IFN-gene products and other TLR7-associated cytokines was observed without increases in NF-κB mediated biosynthesis of proinflammatory cytokines IL-6, TNF⍺, IL-1β
Data demonstrate a favorable safety profile for PRTX007
Full details of the presentation can be found here.

About PRTX007

PRTX007 is Primmune’s lead TherAjuvant, a combination of therapeutic and adjuvant mechanisms of action. PRTX007 is designed to provide immediate benefit to patients through controlled stimulation of the innate immune response while also potentiating long-term effective innate and adaptive immune responses. PRTX007 uniquely engages TLR7 and targeted immune cells without increasing levels of proinflammatory factors like IL-6, TNFα and IL-1β via NF-κB. TherAjuvants differ from other small molecule approaches in that they engage the patient’s immune system rather than acting at virally encoded targets or endogenous tumor cell proteins. PRTX007 is being rapidly advanced towards clinical trials for cancer and viral diseases.

On February 14, 2022 Kinnate Biopharma Inc. (Nasdaq: KNTE) ("Kinnate"), a biopharmaceutical company focused on the discovery and development of small molecule kinase inhibitors for difficult-to-treat, genomically defined cancers, reported that it has been selected to deliver an oral presentation of preclinical data from its KIN-2787 program at the upcoming virtual IASLC 2022 Targeted Therapies of Lung Cancer meeting taking place February 22-26, 2022 (Press release, Kinnate Biopharma, FEB 14, 2022, View Source [SID1234608057]). The presentation will be delivered by study collaborator and presenting author Tadashi Manabe, M.D., Ph.D., Postdoctoral Scholar-Fellow, Department of Medicine, Division of Hematology and Oncology at the University of California, San Francisco (UCSF).

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"We continue to make progress in our clinical trial of KIN-2787 and expect initial data in the third quarter of 2022," said Richard Williams, MBBS, Ph.D., Chief Medical Officer at Kinnate. "Among other indications, KIN-2787 is being developed for the treatment of patients with non-small cell lung cancer driven by BRAF Class II or Class III alterations and we are looking forward to sharing preclinical data on its antitumor activity at this upcoming IASLC meeting."

In this study, KIN-2787 activity was assessed by suppression of downstream MAPK pathway signaling and subsequent cell growth inhibition across BRAF-altered and/or RAS-altered versus wild type panels of human non-small cell lung cancer (NSCLC) cell lines. In contrast to approved therapies, targeting Class I BRAF alterations, KIN-2787 was most active in Class II and Class III BRAF-altered NSCLC cells. KIN-2787 also inhibited cellular proliferation in BRAF alteration-positive human NSCLC cell lines. Additionally, KIN-2787 was active in in vitro cell growth inhibition assays against a parental BRAF Class I-driven NSCLC cell line and retained activity in an experimentally acquired vemurafenib-resistant BRAF p61 splice variant-expressing derived cell line. In vivo, KIN-2787 efficacy was evaluated using a BRAF-alteration driven human NSCLC cell line and patient-derived xenograft models. The ongoing KN-8701 trial (NCT# 04913285) of KIN-2787 is actively enrolling patients across multiple centers in the United States.

"Together, Class II and III alterations represent as many as 65% of all oncogenic BRAF alterations in NSCLC. While there are approved RAF inhibitors being used in combination treatment of BRAF Class I-altered NSCLC, there are currently no RAF-targeted therapies for the treatment of NSCLC patients with tumors driven by BRAF Class II or III alterations, which is likely a contributing factor in the inferior clinical outcomes often seen with these patients," said Dr. Manabe. "I am pleased to share findings from this study which show that KIN-2787 is a potent and selective pan-RAF inhibitor with demonstrated capabilities in overcoming well-characterized resistance mechanisms."

"KIN-2787 is a promising next-generation RAF inhibitor with unique properties that has shown potent activity against a variety of oncogenic BRAF-driven lung cancers in preclinical studies. The preclinical data are exciting, and I have great enthusiasm for its continued clinical development as a potential new targeted therapy that could help address the current unmet needs for oncogene-driven lung cancer patients," added Trever Bivona, M.D., Ph.D., study collaborator and Professor, Hematology and Oncology, at UCSF.

Details of the meeting presentation are as follows:

Abstract title: Antitumor Activity of KIN-2787, a Next-Generation Pan-RAF Inhibitor, in Preclinical Models of Human BRAF-Alteration Driven Non-Small Cell Lung Cancer (NSCLC)
Session: Best Fellows Oral Abstract Session
Session date and time: Wednesday, February 23, 2022 at 4:15pm ET
Additional information on the virtual IASLC 2022 Targeted Therapies of Lung Cancer meeting is available at: View Source