On June 28, 2021 Zentalis Pharmaceuticals, Inc. (Nasdaq: ZNTL), a clinical-stage biopharmaceutical company focused on discovering and developing small molecule therapeutics targeting fundamental biological pathways of cancers, reported key clinical and regulatory updates across its pipeline (Press release, Zentalis Pharmaceuticals, JUN 28, 2021, View Source [SID1234584411]).

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"We continue to build substantial value in Zentalis’ portfolio, driving toward approval of our differentiated cancer therapeutics to help patients worldwide," commented Dr. Anthony Sun, Chairman and Chief Executive Officer of Zentalis. "Based on our clinical results reported to date, the emerging clinical profiles of our candidates support the potential for best-in-class positioning for a range of tumor types addressing large patient populations, is use as a monotherapy or in combinations. In particular, we are excited about the compelling profile of ZN-c3, our WEE1 inhibitor, as it demonstrated additional, deepening and durable tumor responses as a monotherapy in heavily pretreated solid tumors. These promising data set the stage for the many upcoming planned trials – two of which have the potential to be registrational monotherapy studies in indications with significant unmet medical needs. We look forward to a productive second half of 2021, as we focus on delivering on our milestones across our entire pipeline."

ZN-c3: Oral WEE1 Inhibitor for Solid Tumors

Updates from our ongoing trials of ZN-c3 continue to support the potential for our WEE1 inhibitor, ZN-c3, to be both first-in-class and best-in-class. Since our last update at AACR (Free AACR Whitepaper) in April 2021, and as of the data cut-off date of May 15, 2021:

The 2 unconfirmed Partial Responses (PRs) reported at AACR (Free AACR Whitepaper) were confirmed, bringing the total number of confirmed PRs from our monotherapy trial from 3 to 5. Since AACR (Free AACR Whitepaper), an additional unconfirmed PR was reported in a patient with uterine serous carcinoma (USC), resulting in 3 out of 7 USC patients enrolled having responded to treatment. Overall, the objective response rate (ORR) in the USC population increased from 40% to 43% based on RECIST criteria.
Additionally, within the exceptional responder population in the Phase 1 monotherapy trial, we have observed a patient with an ongoing treatment duration of more than 8 months, with a deepening response of 65% to 69% tumor size decrease based on RECIST criteria.
Lower overall severe hematological adverse event rates – severe neutropenia adverse event rates decreased from 2.9% to 2.2% with an additional 11 patients enrolled since AACR (Free AACR Whitepaper) 2021.
Following an End-of-Phase 1 meeting, the U.S. Food and Drug Administration (FDA) concurred in principle with the proposal that ZN-c3 has the potential for an accelerated approval pathway based on the proposed global study design of a Phase 2 monotherapy trial in women with recurrent or persistent USC. The trial has initiated with multiple sites open.
Zentalis is planning to launch a biomarker-driven Phase 2 study pending FDA feedback. The tumor-agnostic trial will investigate ZN-c3 in patients with solid tumors that express the identified predictive biomarker, and is expected to initiate by year-end.
ZN-c3 has received orphan drug designation, and rare pediatric disease designation from the FDA for pediatric osteosarcoma. The Phase 1/2 trial of ZN-c3 in combination with chemotherapy in pediatric patients with osteosarcoma is expected to initiate in 3Q 2021. If ZN-c3 were to obtain approval for the designated indication, it could be eligible for a rare pediatric disease priority voucher upon approval.
Zentalis will also support two planned additional investigator-initiated trials: a trial with the Ivy Brain Center in glioblastoma multiforme (GBM) and a trial with immunotherapy with Dana Farber in triple negative breast cancer.
Zentalis’ China JV Zentera is advancing corresponding clinical trials in China with ZN-c3.
ZN-c5: Oral SERD for ER+/HER2- Advanced or Metastatic Breast Cancer

Based on the interim results from multiple ongoing trials, ZN-c5 has demonstrated the potential to support best-in-class tolerability in both monotherapy and combination settings, with strong clinical results observed. As of May 11, 2021, the following data were collected:

Monotherapy Trials (Expansion and Dose Escalation)

In total, 56 patients with 2 median prior lines of treatment were evaluated for safety and efficacy. Across all doses from 50 mg QD to 300 mg QD, the observed CBR was 33% and the ORR was 5%. ZN-c5 generated 2 PRs at the 150 mg and 300 mg doses. Adverse events (AEs) were found in less than 10% of the patients and there were no observed cases of bradycardia, visual disturbances, QTC or dizziness. Of note, treatment related diarrhea adverse event rate was 3.6%, with only grade 1 or 2 events observed. The Phase 2 monotherapy trial has been initiated and Zentalis may take multiple doses into this study.

An oral dose of 50 mg QD (n=16) demonstrated a CBR of 40%, with many patients in this dose cohort remaining on study drug and in the trial. Final determination of the monotherapy RP2D will occur following completion of this 50 mg QD dose cohort.
Combination Dose Escalation Trials with Pfizer’s CDK4/6 Palbociclib and Lilly’s CDK4 and 6 Abemaciclib

Tolerability data for ZN-c5 suggests it could be best-in-class in oral SERDS, making this candidate ideal for further evaluation in combination. The two separate trials will continue to enroll patients and the Company expects to report interim results in 1H 2022 from one or more of these trials.
Window of Opportunity Trial

The Window of Opportunity trial (n=35) demonstrated ER degradation across all doses tested.
ZN-d5: Highly Selective Oral BCL-2 Inhibitor for Hematologic Tumors

The Phase 1 monotherapy dose-escalation trial, initiated in 4Q 2020, has enrolled 14 patients with relapsed/refractory non-Hodgkin’s lymphoma (NHL) thus far in the fifth dose cohort. Additionally, no dose-limiting toxicities have been identified. Patients with acute myeloid leukemia will begin enrollment in 3Q 2021. Interim results from this Phase 1 trial are expected in 1H 2022.
ZN-e4: 3rd Generation Oral EGFR Inhibitor for Non-Small-Cell Lung Carcinoma

The Phase 1/2 dose-escalation trial in patients with advanced non-small cell lung cancer is ongoing with 26 patients (both osimertinib-naïve and experienced) enrolled to date. ZN-e4 has been well-tolerated at all doses as of the March 25, 2021 data cut-off, and clinical activity was identified at doses greater than 80 mg QD. Interim results from the Phase 1/2 trial are expected in 4Q 2021.
Webcast Event:
Zentalis will host a webcast event today, June 28, 2021 at 8:30 a.m. EDT. To register and access the event, the webcast link is available on the Investors & Media section of the Zentalis website at www.zentalis.com.

On June 28, 2021 Vincerx Pharma, Inc. (Nasdaq: VINC), a biopharmaceutical company aspiring to address the unmet medical needs of patients with cancer through paradigm-shifting therapeutics, reported that the Company has joined the broad-market Russell 3000 and Microcap Indexes as part of the 2021 Russell indexes annual reconstitution, effective after the U.S. market opens today, Monday, June 28, 2021 (Press release, Vincerx Pharma, JUN 28, 2021, View Source [SID1234584409]).

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"Vincerx is pleased to be included in the Russell 3000 and Microcap Indexes, a milestone that highlights our growth since becoming a public company late last year and will broaden our visibility within the investment community," said Ahmed Hamdy M.D., Chief Executive Officer of Vincerx. "Our inclusion in these indexes demonstrates our continued commitment to creating value for our shareholders, and we look forward to continuing our mission of developing innovative targeted oncology therapeutics to transform treatment paradigms for hematological malignancies and solid tumors."

Annual Russell indexes reconstitution captures the 4,000 largest U.S. stocks as of May 7, ranking them by total market capitalization. Membership in the U.S. all-cap Russell 3000 Index, which remains in place for one year, means automatic inclusion in the large-cap Russell 1000 Index or small-cap Russell 2000 Index as well as the appropriate growth and value style indexes. FTSE Russell determines membership for its Russell indexes primarily by objective, market-capitalization rankings and style attributes.

Russell indexes are widely used by investment managers and institutional investors for index funds and as benchmarks for active investment strategies. Approximately $10.6 trillion in assets are benchmarked against Russell’s US indexes. Russell indexes are part of FTSE Russell, a leading global index provider.

For more information on the Russell 3000 Index and the Russell indexes reconstitution, go to the "Russell Reconstitution" section on the FTSE Russell website.

About FTSE Russell:
FTSE Russell is a global index leader that provides innovative benchmarking, analytics and data solutions for investors worldwide. FTSE Russell calculates thousands of indexes that measure and benchmark markets and asset classes in more than 70 countries, covering 98% of the investable market globally.

FTSE Russell index expertise and products are used extensively by institutional and retail investors globally. Approximately $17.9 trillion is currently benchmarked to FTSE Russell indexes. For over 30 years, leading asset owners, asset managers, ETF providers and investment banks have chosen FTSE Russell indexes to benchmark their investment performance and create ETFs, structured products and index-based derivatives.

A core set of universal principles guides FTSE Russell index design and management: a transparent rules-based methodology is informed by independent committees of leading market participants. FTSE Russell is focused on applying the highest industry standards in index design and governance and embraces the IOSCO Principles. FTSE Russell is also focused on index innovation and customer partnerships as it seeks to enhance the breadth, depth and reach of its offering.

FTSE Russell is wholly owned by London Stock Exchange Group.

On June 28, 2021 SHINE Medical Technologies LLC reported that it has closed a $150-million Series C-5 financing (Press release, Shine Medical Technologies, JUN 28, 2021, View Source;pk_kwd=shine-medical-technologies-closes-150-million-series-c-5-financing [SID1234584407]). Koch Disruptive Technologies (KDT) led the round, which also included participation by Fidelity Management & Research Company, Baillie Gifford and other new and current investors . The financing will support SHINE’s commercialization of its diagnostic and therapeutic medical isotope technologies and position the company for future growth as it works toward developing new fusion-based technology applications.

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"KDT is an incredible strategic partner for SHINE as we commercialize both diagnostic and therapeutic medical isotopes, and work towards fusion-based nuclear waste recycling and clean energy production," said Greg Piefer, Chairman and CEO of SHINE. "Koch knows how to scale a company, with more than 120,000 employees around the world, and we look forward to tapping that knowledge as we continue to grow. SHINE’s mission is to usher in a new era of nuclear fusion technology and Koch, which is among the biggest players in energy, is a great long-term, strategic match for us as we pursue our ultimate goal: fusion-based clean energy. We are grateful for their confidence and investment in SHINE."

"SHINE’s innovative medical isotope technologies, which play a crucial role in identifying and treating patients with debilitating diseases, are astounding," said Chase Koch, President of KDT. "We believe SHINE has the potential to change not only the production and supply of medical isotopes, but to transform industrial segments globally by leveraging the company’s nuclear-fusion based technology for industrial inspection and imaging, nuclear waste recycling and energy production. Koch’s global knowledge networks and capabilities are uniquely suited to help SHINE’s impressive team implement its vision to advance fusion technology. We look forward to a productive partnership."

An existing SHINE facility produces the therapeutic medical isotope lutetitum-177 (Lu-177). Radiotherapeutics are one of the fastest growing areas of oncology and has significant potential for the treatment of several cancers because of their ability to directly irradiate cancer including at the late stages. SHINE’s manufacturing process can produce high-specific-activity Lu-177, the form of the isotope most in demand by today’s clinical trial sponsors. Last December, SHINE also broke ground for a large-scale therapeutic isotope plant, which is expected to be operational in mid-2022 and will produce Lu-177.

SHINE is also constructing a U.S. fusion-based medical isotope production facility in Janesville, Wisconsin, to produce molybdenum-99 (Mo-99), which more than 40 million patient procedures rely on each year. There has been little production of Mo-99 in the United States for decades – contributing to chronic shortages of the isotope – and this production facility will be capable of supplying more than one-third of the global demand for Mo-99. SHINE announced in May a location for its new European medical isotope production facility, which when combined with the capacity of SHINE’s U.S. plant will give the company the ability to produce 70 percent of the global patient need for Mo-99. The production facility will be driven by nuclear fusion technology that does not require a reactor and is cleaner, safer and more sustainable than a nuclear research reactor.

"SHINE is grateful for the confidence of our world-class investor syndicate and the ongoing support of our early-stage investors," said Todd Asmuth, SHINE’s President and Chief Strategy Officer. "The support of our institutional and individual investors and local, state and federal partners ensures that SHINE can fully execute its medical isotope plans by building multiple facilities and improving the lives of people around the world. As we bring these production facilities online, we will move into nuclear waste recycling and clean energy production, the next two phases of our plan. By doing so, we will continue to build long-term value for our stakeholders, including our customers, physicians and their patients, our employees and our shareholders."

On June 28, 2021 Sermonix Pharmaceuticals Inc., a privately held biopharmaceutical company developing innovative therapeutics to treat ESR1-mutated metastatic breast and gynecological cancers, reported that enrollment has been completed for its Phase 2 clinical trial collaboration of its lead investigational drug, lasofoxifene, in combination with Eli Lilly and Company’s FDA-approved CDK 4 and 6 inhibitor, abemaciclib (Press release, Sermonix Pharmaceuticals, JUN 28, 2021, View Source [SID1234584406]). Sermonix expects initial data from the trial to be available in the first half of 2022.

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"Combination therapy in the metastatic setting is becoming quite commonplace and the potential to pair a well-tolerated endocrine therapy with a CDK 4/6 inhibitor in women with an ESR1 mutation is important from a clinical perspective, thus it is vital to assess safety and tolerability of these agents used concomitantly to optimize progression-free survival," said Dr. David Portman, Sermonix founder and chief executive officer. "We are delighted to have promptly completed enrollment and thank our participants, their families and clinical centers for supporting our efforts."

The open-label, multi-center study is evaluating the safety of lasofoxifene in combination with abemaciclib for the treatment of pre- and postmenopausal women with locally advanced metastatic estrogen receptor-positive (ER+)/HER2- breast cancer and an ESR1 mutation. It is Sermonix’s second Evaluation ofLasofoxifene inESR1 Mutations (ELAINE) study and is known as ELAINE 2.

Sermonix partnered with Tempus, a technology company advancing precision medicine through the practical application of artificial intelligence in healthcare, to assist in identifying and enrolling patients in the ELAINE 2 study. Leveraging Tempus’ AI capabilities and the TIME Trial program, Sermonix was able to find patients in real-time, especially eligible ESR1+ patients who are treated in the community setting.

Preclinical models of invasive breast cancer at the University of Chicago – recently published in the journal Breast Cancer Research – identified synergy between lasofoxifene, a selective estrogen receptor modulator (SERM), and a CDK 4 and 6 inhibitor in the presence of ESR1 mutations.

"The completion of ELAINE 2 enrollment marks an important preparative step toward conducting a larger efficacy study of lasofoxifene in combination with a CDK 4/6 inhibitor," said Dr. Paul Plourde, Sermonix vice president of clinical development. "We are delighted with the fast study enrollment – particularly given the challenges of the pandemic – and the momentum of lasofoxifene and our ELAINE program as we look to share initial data early in 2022."

For more information about the ELAINE studies, visit View Source

About Lasofoxifene
Lasofoxifene is an investigational, nonsteroidal selective estrogen receptor modulator (SERM), which Sermonix licensed globally from Ligand Pharmaceuticals Inc. (NASDAQ: LGND) and has been studied in previous comprehensive Phase 1-3 non-oncology clinical trials in more than 15,000 postmenopausal women worldwide. Lasofoxifene’s bioavailability and activity in mutations of the estrogen receptor could potentially hold promise for patients who have acquired endocrine resistance due to ESR1 mutations, a common finding in the metastatic setting and an area of high unmet medical need. Lasofoxifene’s novel activity in ESR1 mutations was discovered at Duke University and Sermonix has exclusive rights to develop and commercialize the product in this area. Lasofoxifene, a potent, oral SERM could, if approved, play a critical role in the targeted precision medicine treatment of advanced ER+ breast cancer.

About Abemaciclib
Abemaciclib (trade name Verzenio) is a CDK4 and 6 inhibitor and the first and only oral tablet of its kind that can be taken every day for the treatment of HR+, HER2– metastatic breast cancer. It is indicated for the treatment of HR+, HER2- advanced or metastatic breast cancer, in combination with an aromatase inhibitor for postmenopausal women as initial endocrine-based therapy; in combination with fulvestrant for women with disease progression following endocrine therapy; or as a single agent for adult patients with disease progression following endocrine therapy and prior chemotherapy in the metastatic setting.

On June 28, 2021 Sensei Biotherapeutics, an immunotherapy company focused on the discovery and development of next generation therapeutics for cancer, reported that it is reprioritizing its pipeline programs to focus on its product candidates, including its multi-antigenic next generation ImmunoPhage candidate, now referred to as SNS-401-NG, and its monoclonal antibody SNS-VISTA (V-set Immunoglobulin Domain Suppressor of T cell Activation) candidate (Press release, Sensei Biotherapeutics, JUN 28, 2021, View Source [SID1234584405]). With this reallocation of resources, Sensei expects its cash and cash equivalents will be sufficient to fund its operations into the first half of 2024.

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"Sensei’s approach to drug development is deeply rooted in targeting key mechanisms of checkpoint resistance to induce a robust, focused and coordinated immune response to cancer. We believe our next generation, multi-antigenic ImmunoPhage product candidates have the potential to drive robust antigen-specific T cell responses that will translate into clinical benefit," said John Celebi, president and chief executive officer of Sensei Biotherapeutics. "Given the totality of data generated to-date from the Phase 1/2 combination trial of first-generation SNS-301, we believe we have captured important insights into the power of our ImmunoPhage platform that will further advance development of our pipeline product candidates. Through SNS-301, we have gained important information on key product attributes that we believe contribute to the safety and immunogenicity of our ImmunoPhage platform as well as how to manufacture and scale our product candidates. Specifically, we have learned that the use of gpD fusion as an antigen display technology is suboptimal for use in an active cancer vaccine. We believe the incorporation of new antigen attachment technologies will ensure optimal immunogenicity. We are excited by our next generation programs, and we look forward to further advancing our two ongoing programs SNS-401-NG and SNS-VISTA into the clinic and completing discovery work for our VSIG4 antibody program."

"I would like to express my gratitude to all of the patients and their families, investigators and collaborators who participated in the SNS-301 study," said, Marie-Louise Fjaellskog, M.D., Ph.D. chief medical officer of Sensei Biotherapeutics. "Our data-driven decision-making process is at the forefront of our work, and we are well positioned and capitalized to further progress our next-generation pipeline programs, SNS-401-NG and SNS-VISTA, by utilizing our two unique drug discovery approaches – our ImmunoPhage platform and our monoclonal antibody and nanobody platform. We look forward to initiating IND-enabling studies for SNS-VISTA by the end of 2021 and for SNS-401-NG in second half of 2022."

SNS-301 was developed as a first-generation, bio-engineered, inactivated bacteriophage virus expressing a fragment of the tumor-associated antigen, human aspartate β-hydroxylase (ASPH), as a fusion protein to the bacteriophage lambda capsid decoration protein, gpD, for patients with locally advanced unresectable or metastatic squamous cell head and neck cancer (SCCHN). To date, 25 patients were enrolled in the Phase 1/2 clinical study and received at least one dose of SNS-301 in combination with pembrolizumab; one patient had a deep and durable partial response (PR) and 8 patients had stable diseases. While encouraged by the safety profile of the SNS-301 single antigen approach, based upon the recent analysis of antigen specific T-cell activation which did not show a significant increase in ASPH-specific T cells, including the one patient who experienced a long-standing and deep PR, and an updated analysis of clinical data, Sensei has decided to reprioritize its pipeline and refocus resources. Sensei anticipates sharing full SNS-301 clinical data and the results of specific B and T cell response data at a future scientific conference.

Next-Generation Pipeline Highlights and Upcoming Milestones

Sensei is focused on progressing novel product candidates generated from both its ImmunoPhage platform and Phortress Library, coupled with its human monoclonal antibody and nanobody platform. Sensei’s Phortress Library of immunophages, derived from antigens found across multiple patient populations and tumor types, enables a personalized, yet off-the-shelf therapeutic option to patients.

SNS-401-NG is a first-in-class, multi-antigenic personalized ImmunoPhage candidate being developed in collaboration with the University of Washington. Sensei has designed SNS-401-NG as a personalized product candidate composed of premanufactured Immunophage from Sensei’s Phortress library on an improved and proprietary bacteriophage construct. Sensei intends to initiate IND-enabling studies for this product candidate in the second half of 2022. The first clinical application is directed to the treatment of Merkel Cell Carcinoma (MCC), an aggressive form of skin cancer commonly driven by the Merkel Cell Polyoma Virus. If clinical proof of concept is achieved, Sensei plans to evaluate a broader basket study in patients with head and neck cancer, lung cancer, melanoma, and triple negative breast cancer based on the prevalence of Phortress antigens.
VISTA (V-domain Ig suppressor of T cell activation) is an immune checkpoint that inhibits anti-tumor immune responses. VISTA is implicated in PD-1/PD-L1 resistance and therapeutic intervention. VISTA has the potential to be effective as a monotherapy and synergistic with PD-1/PD-L1 inhibition. Sensei has generated potent pH-dependent parental antibodies that block the interaction of VISTA with its receptor, PSGL1, expected to result in a favorable pharmacokinetic (PK) profile and selective activity in the acidic tumor microenvironment – a critical feature of this product candidate, and an important differentiator to other compounds in development targeting VISTA. Sensei plans to present preclinical data from the SNS-VISTA program at a scientific conference in 2021 and to initiate IND-enabling studies by the end of 2021.
VSIG4 (V-Set And Immunoglobulin Domain Containing 4) is a potent inhibitor of T cell activity, often overexpressed on macrophages within the tumor microenvironment. Sensei believes that a tumor-selective blocking monoclonal antibody will have potent anti-tumor immune effects. Sensei is extending its approach to developing antibodies with enhanced tumor selective activity to other candidate immune checkpoint targets, and anticipates selecting a product candidate from this program in 2023.
Conference Call and Webcast Information

Sensei will host a live conference and webcast today, June 28, 2021, at 4:30 p.m. ET, to discuss these company updates. To access the conference call, please dial 833-362-0204 (domestic) or 914-987-7673 (international) and refer to conference ID number 7464477. The live webcast can be accessed under the "Events & Presentations" section of Sensei’s website at www.senseibio.com. The webcast will be archived and made available for replay on Sensei’s website approximately two hours after the call and will be available for 30 days.