On May 5, 2022 BridgeBio Pharma, Inc. (Nasdaq: BBIO) (BridgeBio or the Company), a commercial-stage biopharmaceutical company focused on genetic diseases and cancers, reported its financial results for the first quarter ended March 31, 2022 and provided an update on the Company’s operations (Press release, BridgeBio, MAY 5, 2022, View Source [SID1234613613]).

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"Building on our positive Phase 2 data in LGMD2i, we are excited for a summer of ongoing focused execution where we have the opportunity to deliver meaningful data in two additional large conditions with great unmet need: ADH1 and achondroplasia," said Neil Kumar, Ph.D., founder and CEO of BridgeBio.

BridgeBio’s key programs:

Acoramidis (AG10) – Transthyretin (TTR) stabilizer for transthyretin amyloid cardiomyopathy (ATTR-CM): The Company released updated data from its ongoing Phase 2 open-label extension (OLE) study of acoramidis in patients with ATTR-CM, which demonstrated that acoramidis continued to be well-tolerated and potently stabilize TTR. NT-proBNP, a biomarker of cardiac failure and independent predictor of mortality in ATTR-CM patients, was stable or improving throughout the study and serum TTR levels were sustainably increased from baseline at Month 30. Topline data from the Month 30 primary endpoint of the ongoing Phase 3 trial of acoramidis in ATTR-CM (ATTRibute-CM), a hierarchical composite including all-cause mortality and cardiovascular hospitalizations, are expected in mid-2023.

Encaleret – Calcium-sensing receptor (CaSR) inhibitor for autosomal dominant hypocalcemia type 1 (ADH1): Data from BridgeBio’s Phase 2b study of encaleret in ADH1 to be presented at the Endocrine Society’s 2022 ENDO conference in Atlanta from June 11-14, 2022. The planned presentation will include the profile of encaleret on clinically relevant mineral homeostasis parameters over 24 weeks of outpatient evaluation. Achieving simultaneous blood and urine calcium normalization is a challenge for patients with ADH1 due to the limitations of the current standard of care. If approved, encaleret could be the first therapy indicated for the treatment of ADH1, a condition caused by gain of function variants of the CASR gene estimated to be carried by 12,000 individuals in the United States alone. The Company intends to initiate a Phase 3 registrational trial of encaleret in patients with ADH1 in 2022 and anticipates Phase 3 topline data in 2023. Issued and filed patents are expected to provide market protection for encaleret in ADH1 to 2041.

Low-dose infigratinib – FGFR1-3 inhibitor for achondroplasia and hypochondroplasia: Initial data from the ongoing Phase 2 dose-escalation and expansion study is anticipated in mid-2022. The Company also plans to share multiple presentations at the Endocrine Society’s 2022 ENDO conference in Atlanta from June 11-14, 2022, including preclinical data for low-dose infigratinib in a mouse model of hypochondroplasia (an FGFR3-driven skeletal dysplasia), new analyses of natural history data in achondroplasia, and the results of a qualitative research study conducted to identify concepts and quality-of-life questionnaires relevant for the achondroplasia community. Achondroplasia is the most common form of genetic short stature and one of the most common genetic diseases, with a prevalence of over 55,000 cases in the United States and European Union. Low-dose infigratinib is the only known product candidate in clinical development for achondroplasia that is designed to target the disease at its genetic source and the only orally administered product candidate in clinical development for achondroplasia.

BBP-631 – AAV5 gene therapy candidate for congenital adrenal hyperplasia (CAH): Dosed first patient in Phase 1/2 gene therapy trial in January 2022. Initial Phase 1/2 data readout anticipated in second half of 2022. CAH is one of the most prevalent genetic diseases potentially addressable with adeno-associated virus (AAV) gene therapy, with more than 75,000 cases estimated in the United States and European Union. The disease is caused by deleterious mutations in the gene encoding an enzyme called 21-hydroxylase, leading to a lack of endogenous cortisol production. BBP-631 is designed to provide a functional copy of the 21-hydroxylase-encoding gene (CYP21A2) and potentially address many aspects of the disease course.

BBP-418 – Glycosylation substrate for limb-girdle muscular dystrophy type 2i (LGMD2i): Announced positive Phase 2 data at the Muscular Dystrophy Association 2022 Annual Meeting on March 14, 2022. BridgeBio plans to engage with regulatory health bodies in 2022 to discuss potential paths to approval and subsequently intends to initiate a Phase 3 clinical trial. If successful, BBP-418 could be the first approved therapy for patients with LGMD2i. BridgeBio believes its initial Phase 2 results indicate the potential for BBP-418 to increase glycosylation of αDG and drive functional improvements for patients, as well as reduce CK, a key marker of muscle breakdown. Furthermore, the 90- and 180-day data show improvements on walk tests from baseline, which the Company believes suggests a potential impact on clinical function and on the rate of disease progression.

RAS cancer portfolio: BridgeBio expects to select a RAS development candidate in 2022. It previously announced the discovery of its next-generation KRAS G12C dual inhibitors, the first-known compounds that directly bind and inhibit KRAS in both its active (GTP bound) and inactive (GDP bound) conformations, and PI3ka:RAS breakers, small molecules that block RAS driven PI3Ka activation – a novel approach with the potential to inhibit oncogenic PI3Ka signaling without adverse effects on glucose metabolism. RAS is one of the most well-known oncogenic drivers with approximately 30% of all cancers being driven by RAS mutations, including large proportions of lung, colorectal and pancreatic tumors.

Recent corporate updates

Sale to Sentynl Therapeutics, Inc., of NULIBRY (Fosdenopterin) for Injection: Sentynl has acquired global rights to NULIBRY and will be responsible for the ongoing development and commercialization of NULIBRY in the United States and developing, manufacturing and commercializing fosdenopterin globally. BridgeBio will share development responsibilities for fosdenopterin through approval of the marketing authorization application already under accelerated assessment with the European Medicines Agency and through approval of its regulatory submission with the Israeli Ministry of Health. Sentynl will provide cash payments upon the achievement of certain regulatory milestones. BridgeBio will be eligible to receive commercial milestone payments as well as tiered royalties on adjusted net sales of NULIBRY. NULIBRY is approved by the U.S. Food and Drug Administration (FDA) to reduce the risk of mortality in patients with molybdenum cofactor deficiency Type A, an ultra-rare, life-threatening pediatric genetic disorder.

Updated strategic collaboration with Helsinn Group to develop, manufacture and commercialize infigratinib in oncology indications in the U.S.: Under the terms of the amended and restated agreement, Helsinn will gain an exclusive license to commercialize infigratinib in the United States and will be responsible for developing, manufacturing and commercializing infigratinib in oncology indications worldwide except for achondroplasia or any other skeletal dysplasias, and except in mainland China, Hong Kong and Macau. BridgeBio will be eligible to receive regulatory and commercial milestone payments as well as tiered royalties on adjusted net sales from Helsinn. BridgeBio will retain all rights to develop, manufacture and commercialize infigratinib in skeletal dysplasia, including achondroplasia. In 2021, Helsinn and BridgeBio obtained accelerated approval for TRUSELTIQ (infigratinib) from the FDA for the treatment of adults with previously treated, unresectable locally advanced or metastatic cholangiocarcinoma with a fibroblast growth factor receptor 2 fusion or other rearrangement as detected by an FDA-approved test.

Business development – Due to the need to conserve capital and prioritize focused execution, BridgeBio is engaged in partnering and out-licensing discussions for the following programs:

BBP-589 – Recombinant collagen 7 for dystrophic epidermolysis bullosa
Completed Phase 2 clinical trial evaluating safety and tolerability of BBP-589, as well as clinical proof-of-concept, and initiated a Phase 2 extension study
BBP-681 – Topical PI3KA inhibitor for venous and lymphatic malformations
Phase 1/2 clinical trial underway
BBP-561 – KLK 5/7 inhibitor for Netherton syndrome
Investigational New Drug application (IND) enabling studies underway
BBP-815 – AAV gene therapy for nonsyndromic hearing loss
Preclinical development
BBP-818 – AAV gene therapy for classic galactosemia
IND-enabling studies underway
BBP-472 – PI3KB inhibitor for PTEN autism
Preclinical development

First Quarter 2022 Financial Results:

Cash, Cash Equivalents and Marketable Securities

Cash, cash equivalents and marketable securities, excluding restricted cash, totaled $633.5 million as of March 31, 2022, compared to $787.5 million as of December 31, 2021. The net decrease of $154.0 million pertains primarily to payments for operating costs and expenses of $160.6 million, which includes $18.8 million in payments for debt-related interests, timing of payments of accrued compensation and benefits of $16.9 million and $3.9 million in payments related to the restructuring initiative that the Company implemented during the current quarter as described below. During the current quarter, the Company received an upfront payment of $10.0 million upon closing of the asset purchase agreement between its affiliate, Origin Biosciences, and Sentynl Therapeutics.

"We made significant progress in reducing our expenditures in the first quarter, highlighted by a combined reduction of over $100 million in 2022-2023 operating expenses through the Helsinn and Sentynl deals, but we are not yet done. Our priorities are focusing resources towards select internal programs while finding value-creating partnerships for others that we believe allow science to advance seamlessly towards patients. Our expectation is that operating expenses and cash burn will meaningfully decline in the second quarter as restructuring charges from the beginning of the year decline and anticipated additional business development activity allows us to decrease further from that baseline, establishing a reduced run rate for the rest of the year. We currently expect to have runway up to and beyond the readout of our ATTR catalyst in mid-2023 without requiring equity dilution. We reiterate our guidance of runway into 2024," said Brian Stephenson, Ph.D., CFA, BridgeBio’s Chief Financial Officer.

BridgeBio is engaged in partnering and out-licensing discussions for a select number of programs, which are listed on the Company’s website.

Operating Costs and Expenses

Operating costs and expenses increased by $7.4 million to $175.4 million for the first quarter of 2022 as compared to $168.0 million for the same period in the prior year. During the current quarter, the Company incurred $22.7 million in restructuring, impairment and related charges, as part of its restructuring initiative. In January 2022, the Company committed to a restructuring initiative designed to drive operational changes in its business processes, efficiencies and cost savings to advance corporate strategy and development programs. The restructuring initiative included, among other components, consolidation and rationalization of facilities, reprioritization of development programs and the reduction of our workforce. The Company has substantially completed the activities and has incurred most of the costs related to the restructuring initiative during the current quarter. The Company estimates to incur total charges in the range of approximately $23.0 million to $25.0 million for the fiscal year 2022, consisting primarily of impairments and write-offs of long-lived assets, severance and employee-related costs, and exit and other related costs. The estimate of the range of costs is subject to certain assumptions, such as the Company’s ability to sublease certain office spaces. Actual results may differ from those estimates or assumptions. The nonrecurring charges related to the restructuring initiative were partially offset by a $15.3 million decrease in the Company’s normal operating expenses compared to the same period in the prior year, primarily due to cost savings and impacts from such restructuring initiative.

The Company’s research and development expenses have not been significantly impacted by the global COVID-19 pandemic for the periods presented. While BridgeBio experienced some delays in certain of its clinical enrollment and trial commencement activities, it continues to adapt in this unprecedented time to enable alternative site, telehealth and home visits, at-home drug delivery, as well as mitigation strategies with its contract manufacturing organizations. The longer-term impact, if any, of COVID-19 on BridgeBio’s operating costs and expenses is currently unknown.

On May 5, 2022 Elevation Oncology, Inc. (Nasdaq: ELEV), a clinical stage biopharmaceutical company focused on the development of precision medicines for patients with genomically defined cancers, reported financial results for the quarter ended March 31, 2022, and highlighted recent progress (Press release, Elevation Oncology, MAY 5, 2022, https://elevationoncology.com/elevation-oncology-reports-first-quarter-2022-financial-results-and-highlights-recent-company-progress/?utm_source=rss&utm_medium=rss&utm_campaign=elevation-oncology-reports-first-quarter-2022-financial-results-and-highlights-recent-company-progress [SID1234613642]).

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"CRESTONE is an important study for both Elevation Oncology and for patients with NRG1 fusions, a genomically defined patient population with no approved therapies addressing the unmet medical need. We are honored for the opportunity to share the initial and first ever clinical data of seribantumab in this patient population through an oral presentation at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) 2022 Annual Meeting in June 2022." said Shawn M. Leland, PharmD, RPh, Founder and Chief Executive Officer of Elevation Oncology. "In addition to executing on CRESTONE, we are building an industry-leading team, led by people like Dr. David Dornan, our newly appointed Chief Scientific Officer, who brings a wealth of cancer drug development experience to advance our mission of maximizing the potential of seribantumab and building out an industry-leading precision oncology pipeline. Together with our diagnostic and academic partners, we look forward to advancing the field of precision oncology by expanding upon our operational platform and continuing to make genomic testing results therapeutically actionable."

Recent Progress and Highlights
Seribantumab

Initial CRESTONE data selected for oral presentation at ASCO (Free ASCO Whitepaper) 2022. ASCO (Free ASCO Whitepaper) abstracts to be published on May 26, 2022 at 5:00PM ET. The presentation, scheduled for June 7, 2022, from 9:45AM-12:45PM CT, will highlight initial clinical data from approximately 10 patients from Cohort 1 in the ongoing Phase 2 CRESTONE study evaluating seribantumab at 3 grams weekly in patients with solid tumors harboring NRG1 gene fusions.
Corporate

David Dornan, PhD appointed Chief Scientific Officer. In March, Elevation Oncology announced the appointment of Dr. Dornan, PhD, as the Company’s first Chief Scientific Officer, bringing deep oncology R&D and drug development expertise and further strengthening the leadership team.
Expected Upcoming Milestones and Operational Objectives
Initial Phase 2 CRESTONE data to be presented in an oral presentation at ASCO (Free ASCO Whitepaper) 2022
Complete enrollment of the first 20 patients in Cohort 1 of the CRESTONE study in mid-2022
Ongoing target evaluation and continued execution of our strategy for future pipeline expansion
First Quarter 2022 Financial Results
As of March 31, 2022, the Company had cash, cash equivalents and marketable securities totaling $132.1 million, compared to $146.3 million as of December 31, 2021.

Research and development expenses for the first quarter 2022 were $13.6 million, compared to $4.1 million for the first quarter 2021. The increase in R&D expense was primarily related to an increase in manufacturing, personnel costs and other expenses associated with the CRESTONE study.

General and administrative expenses for the first quarter 2022 were $3.8 million, compared to $1.0 million for the first quarter 2021. The increase in G&A expense was primarily related to personnel costs, professional services and other administrative costs.

Net loss for the first quarter 2022 was $17.3 million, compared to $5.1 million for the first quarter 2021.

Financial Outlook
Elevation Oncology expects its existing cash, cash equivalents and marketable securities as of March 31, 2022 will be sufficient to fund its current operations into the fourth quarter of 2023.

About Seribantumab and NRG1 Gene Fusions
Seribantumab is a fully human IgG2 monoclonal antibody that binds to human epidermal growth factor receptor 3 (HER3). HER3 is traditionally activated through binding of its primary ligand, neuregulin-1 (NRG1). The NRG1 gene fusion is a rare genomic alteration that combines NRG1 with another partner protein to create chimeric NRG1 "fusion proteins." The NRG1 fusion protein is often also able to activate the HER3 pathway, leading to unregulated cell growth and proliferation. Importantly, NRG1 gene fusions are predominantly mutually exclusive of other known genomic driver mutations and are considered a unique oncogenic driver event associated with tumor cell survival.

NRG1 fusions have been identified in a variety of solid tumors, including lung, pancreatic, gallbladder, breast, ovarian, colorectal, neuroendocrine, cholangiocarcinomas, and sarcomas. In preclinical experiments, seribantumab prevented the activation of HER3 signaling in cells that harbor an NRG1 gene fusion and destabilized the entire ERBB family signaling pathway, including the activation of HER2, EGFR, and HER4. In addition to extensive nonclinical characterization and testing, seribantumab has been administered to more than 800 patients across twelve Phase 1 and 2 studies, both as a monotherapy and in combination with various anti-cancer therapies. Seribantumab is currently being evaluated in the Phase 2 CRESTONE study for patients with solid tumors of any origin that have an NRG1 fusion.

About the Phase 2 CRESTONE Study
Clinical Study of Response to Seribantumab in Tumors with Neuregulin-1 (NRG1) Fusions (CRESTONE) is a Phase 2 tumor-agnostic "basket trial" evaluating the safety and efficacy of seribantumab in patients with solid tumors that harbor an NRG1 fusion and have progressed after at least one prior line of standard therapy. The primary objective of the study is to describe the anti-tumor activity and safety of seribantumab as a monotherapy specifically in patients whose solid tumor is uniquely driven by an NRG1 gene fusion. CRESTONE offers a clinical trial opportunity for patients with advanced solid tumors who have not responded or are no longer responding to treatment. Patients are encouraged to talk to their doctor about genomic testing of their tumor. CRESTONE is open and enrolling patients in the United States, Australia, and Canada. For more information visit www.NRG1fusion.com.

On May 5, 2022 Corvus Pharmaceuticals, Inc. (Corvus or the Company) (Nasdaq: CRVS), a clinical-stage biopharmaceutical company, reported financial results for the quarter ended March 31, 2022 (Press release, Corvus Pharmaceuticals, MAY 5, 2022, View Source [SID1234613657]).

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"We are advancing our three clinical product candidates according to a clear strategy focused on the interaction of tumors with the immune system," said Richard A. Miller, M.D., co-founder, president and chief executive officer of Corvus. "Our product candidates have demonstrated enhanced immune responses to a wide range of solid and hematologic cancers and are designed to act alone or in combinations. We are a leader in the modulation of CD73 and adenosine to affect tumor immunity, with mid-to-late stage clinical trials for mupadolimab and ciforadenant on track for initiation later this year. In addition, we have demonstrated encouraging potential of our ITK inhibitor on T cell differentiation, raising important new potential applications in cancer and autoimmune diseases."

2022 Key Areas of Focus
Corvus is advancing three clinical programs in 2022, including plans for a Phase 2 study for mupadolimab in front-line non-small cell lung cancer (NSCLC), a Phase 1b/2 study for ciforadenant in front-line renal cell cancer (RCC), and the ongoing Phase 1/1b study for CPI-818 in T-cell lymphoma.

The Company will host an R&D Symposium on Tuesday, May 10, 2022 to provide an update on these clinical programs. The event will take place in New York City from 9:00 – 11:30 am Eastern Time. A webcast of the event will be available on the Corvus website at www.corvuspharma.com.

Mupadolimab (anti-CD73)

The Company continues to enroll its two Phase 1b/2 clinical trial expansion cohorts of patients with (1) head and neck cancers that have failed previous treatment with anti-PD-1 therapy and chemotherapy and (2) relapsed refractory NSCLC who have failed previous treatment with anti-PD(L)-1 therapy and chemotherapy. Up to 15 patients will be enrolled in each expansion cohort and treated with the combination of mupadolimab and pembrolizumab.
The Company plans to initiate a randomized Phase 2 clinical trial evaluating mupadolimab as a front-line therapy for the treatment of patients with advanced NSCLC later this year. The randomized, blinded clinical trial will compare standard chemotherapy plus pembrolizumab (anti-PDL-1) with or without mupadolimab. The Company intends to enroll approximately 150 patients with any tumor PDL-1 expression in the clinical trial, potentially addressing a large patient population. The primary endpoint for the study will be progression free survival and secondary endpoints will evaluate objective response rate and overall survival.
Ciforadenant (adenosine 2a receptor antagonist)

The Company plans to collaborate with the Kidney Cancer Clinical Trials Consortium to initiate an open-label Phase 2 clinical trial evaluating ciforadenant as a first-line therapy for metastatic RCC in combination with ipilimumab (anti-CTLA-4) and nivolumab (anti-PD-1). The clinical trial, which is anticipated to be initiated in the third quarter 2022, will enroll up to 60 patients and is intended to evaluate the potential for ciforadenant to generate increased complete responses and deep responses in the front-line setting. The Kidney Cancer Clinical Trials Consortium is comprised of a group of leading cancer centers in the United States led by investigators at MD Anderson. The trial design is based on Corvus’ preclinical research published in 2018 in Cancer Immunology Research that demonstrated impressive antitumor control and cures in several animal models using ciforadenant in combination with anti-CTLA4 and anti-PD1.
CPI-818 (selective ITK inhibitor)

Corvus and its partner in China, Angel Pharmaceuticals, are enrolling patients with relapsed T cell lymphomas in Phase 1/1b trial evaluating single agent therapy with CPI-818. Angel Pharmaceuticals is responsible for all expenses related to conducting the clinical trial in China. Monitoring of immune modulation of normal T cells as well as safety and anti-tumor activity are being assessed in the clinical trial, with data expected later this year. Based on interim results observed in patients with peripheral T cell lymphoma (PTCL) in these Phase 1/1b clinical trials, the Company believes such results could provide the foundation for a potential global phase 2 clinical trial in advanced PTCL.
Financial Results
As of March 31, 2022, Corvus had cash, cash equivalents and marketable securities totaling $62.9 million. This compared to cash, cash equivalents and marketable securities of $69.5 million as of December 31, 2021.

Research and development expenses for the three months ended March 31, 2022 totaled $5.1 million compared to $8.2 million for the same period in 2021. The decrease of $3.1 million was primarily due to lower outside clinical trial and personnel costs.

The net loss for the three months ended March 31, 2022 was $8.3 million compared to a net loss of $11.6 million for the same period in 2021. Total stock compensation expense for the three months ended March 31, 2022 was $0.7 million compared to $1.2 million for the same period in 2021 and the non-cash loss from our equity method investment in Angel Pharmaceuticals was $1.0 million for the three months ended March 31, 2022 compared to $0.1 million in the same period in 2021.

About Corvus Pharmaceuticals
Corvus Pharmaceuticals is a clinical-stage biopharmaceutical company. Corvus’ lead product candidate is mupadolimab (CPI-006), a humanized monoclonal antibody directed against CD73 that has exhibited immunomodulatory activity and activation of immune cells in preclinical and clinical studies. The Company’s second clinical program, CPI-818, is an investigational, oral, small molecule drug that selectively inhibited ITK in preclinical studies and is in a multicenter Phase 1/1b clinical trial in patients with several types of T-cell lymphomas. Its third clinical program, ciforadenant (CPI-444), is an oral, small molecule inhibitor of the A2A receptor. For more information, visit www.corvuspharma.com.

About Mupadolimab
Mupadolimab (CPI-006) is an investigational, potent humanized monoclonal antibody that is designed to react with a specific site on CD73. In preclinical studies, it has demonstrated immunomodulatory activity resulting in activation of lymphocytes, induction of antibody production from B cells and effects on lymphocyte trafficking. While there are other anti-CD73 antibodies and small molecules in development for treatment of cancer, such agents react with a different region of CD73. Mupadolimab is designed to react with a region of the molecule that acts to stimulate B cells and block production of immunosuppressive adenosine. Mupadolimab is being studied in combination with pembrolizumab in a Phase 1b/2 clinical trial in patients with advanced head and neck cancers and in patients with NSCLC that have failed chemotherapy and anti-PD(L)1 therapy. It is postulated that the activation of B cells will enhance immunity within the tumors of these patients, leading to improved clinical outcomes.

About CPI-818
CPI-818 is an investigational small molecule drug given orally that has selectively inhibited ITK (interleukin-2-inducible T-cell kinase) in preclinical studies. It was designed to possess dual properties: to block malignant T-cell growth and to modulate immune responses. ITK, an enzyme, is expressed predominantly in T-cells and plays a role in T-cell and natural killer (NK) cell lymphomas and leukemias, as well as in normal immune function. Interference with ITK signaling can modulate immune responses to various antigens. The Company believes the inhibition of specific molecular targets in T-cells may be of therapeutic benefit for patients with T-cell lymphomas and leukemias and in patients with autoimmune diseases. The Company is conducting a Phase 1/1b trial in patients with refractory T-cell lymphomas that was designed to select the optimal dose of CPI-818 and evaluate its safety, PK, target occupancy, biomarkers and efficacy. Interim data from the Phase 1/1b clinical trial of CPI-818 for T cell lymphoma demonstrated tumor responses in very advanced, refractory, difficult to treat T cell malignancies.

About Ciforadenant
Ciforadenant (CPI-444) is an investigational small molecule, oral, checkpoint inhibitor designed to disable a tumor’s ability to subvert attack by the immune system by blocking the binding of adenosine in the tumor microenvironment to the A2A receptor. Adenosine, a metabolite of ATP (adenosine tri-phosphate), is produced within the tumor microenvironment where it may bind to the adenosine A2A receptor present on immune cells and block their activity.

On May 5, 2022 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 financial results for the first quarter ended March 31, 2022 and highlighted recent corporate accomplishments (Press release, Zentalis Pharmaceuticals, MAY 5, 2022, View Source [SID1234613673]).

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"In the first quarter of 2022, we achieved multiple clinical milestones and expanded our strategic partnerships with industry leaders," commented Dr. Anthony Sun, Chairman and Chief Executive Officer of Zentalis. "Most recently at AACR (Free AACR Whitepaper), we shared promising clinical data on ZN-c3 – our potentially best-in-class Wee1 inhibitor – from two ongoing trials, in addition to preclinical data on its potential in settings including AML, PARP-resistant ovarian cancer, and in combination with ZN-d5, our BCL-2 inhibitor. The urgency for novel, tolerable treatments that address cancer patients’ unmet needs remains high, and we have prioritized the development of ZN-c3 and ZN-d5, as we are confident in their ability to fill treatment gaps for a range of solid and liquid tumors. Furthermore, we are thrilled to partner with Pfizer and Caris Life Sciences and are grateful for their support as we work toward delivering differentiated oncology candidates to patients in need."

Program Highlights:

In April 2022, Zentalis presented five abstracts at the American Association of Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting and held a webcast event with Key Opinion Leader, Kathleen Moore, M.D., to further discuss the clinical and preclinical data. Additional details on the data presented at the AACR (Free AACR Whitepaper) conference are available here.
In March 2022, Zentalis announced the first patient was dosed in the potentially registrational Phase 1/2 study of ZN-d5, the Company’s BCL-2 inhibitor, in patients with relapsed or refractory light chain (AL) amyloidosis. The trial is a global, single arm, open-label study evaluating the safety, tolerability, pharmacokinetics, pharmacodynamics and efficacy of ZN-d5.
In March 2022, Zentalis announced a strategic collaboration with Caris Life Sciences, the leading molecular science and technology company actively developing and delivering innovative solutions to revolutionize healthcare. Utilizing its molecular profiling platforms, Caris will help identify and characterize patients for Zentalis’ clinical studies, initially for clinical trials investigating ZN-c3.
Corporate Highlights:

In April 2022, the Company sold 953,834 of its common shares at a price of $26.21 per share to Pfizer for gross proceeds of approximately $25.0 million. Zentalis and Pfizer plan to jointly advance the clinical development of ZN-c3. In addition, Zentalis intends to use the net proceeds to fund ongoing and planned clinical trials, including studies of ZN-c3 and ZN-d5 and for working capital and general corporate purposes.
Adam Schayowitz, Ph.D., MBA, Vice President & Medicine Team Group Lead for Breast Cancer, Colorectal Cancer and Melanoma, Pfizer, has joined Zentalis’ Scientific Advisory Board. Dr. Schayowitz will work closely with Zentalis’ senior management team to provide input on the Company’s clinical strategy.
In March 2022, Zentalis announced it contributed $1 million to the Stand Up to Cancer (SU2C) Catalyst program to support research that investigates certain small molecule inhibitors for the treatment of various cancer types.
First Quarter 2022 Financial Results

Cash and Marketable Securities Position: As of March 31, 2022, Zentalis had cash, cash equivalents and marketable securities of $289.4 million. The Company believes that its existing cash, cash equivalents and marketable securities as of March 31, 2022, together with approximately $24.7 million of net proceeds from the April 2022 Pfizer equity investment, prioritization of the clinical development of ZN-c3 and ZN-d5, and budget reallocation, will be sufficient to fund its operating expenses and capital expenditures requirements into the first quarter of 2024.
Research and Development Expenses: Research and development expenses for the three months ended March 31, 2022 were $46.1 million, compared to $38.4 million for the three months ended March 31, 2021. The increase was primarily due to increases in external research and development expenses related to Zentalis’ clinical product candidates as the Company advanced its clinical pipeline and personnel costs.
General and Administrative Expenses: General and administrative expenses for the three months ended March 31, 2022 were $11.8 million, compared to $12.0 million during the three months ended March 31, 2021. The decrease in expenses was primarily attributable to allocable expenses and stock based compensation.

On May 15, 2022 Elpiscience Biopharmaceuticals, Inc. ("Elpiscience"), a clinical-stage biopharmaceutical company focused on developing next-generation immunotherapies to benefit cancer patients worldwide, reported partner Compass Therapeutics reported positive interim ES104 (also known as CTX-009) Phase 2 data in combination with paclitaxel in patients with biliary tract cancers (BTC) (Press release, Elpiscience, MAY 5, 2022, View Source [SID1234613705]). ES104 is a bispecific antibody that simultaneously blocks Delta-like ligand 4/Notch (DLL4) and vascular endothelial growth factor A (VEGF-A) signaling pathways, which are critical to angiogenesis and tumor vascularization.

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In the study, ES104 demonstrated:

42% overall response rate (ORR) based on 10 patients with Partial Responses (PRs), including 9 PRs confirmed by RECIST 1.1 and 1 PR pending confirmation
Anti-tumor activity in previously treated patients with a clinical benefit rate (CBR) of 92% based on 22 patients with a PR or stable disease (SD) out of 24 enrolled patients
Well-tolerated and preliminary safety profile consistent with prior studies
The Phase 2 study in patients with BTC is currently being conducted at four leading medical centers in Korea and Compass Therapeutics plans to open additional sites in the United States. In China, Elpiscience is currently enrolling patients in a ES104 Phase 1/2 study for the treatment of unresectable locally advanced or metastatic colorectal cancer (CRC). ES104 is currently the only clinical-stage bispecific antibody targeting VEGF and DLL4 in China.

"We are encouraged by the impressive interim Phase 2 data in BTC patients from our partner," said Steve Chin, Chief Medical Officer of Elpiscience. "ES104 in combination with paclitaxel showed a high ORR including responses in all four BTC subtypes and good overall tolerability consistent with prior studies. We believe in the clinical strategy to simultaneously target VEGF and DLL4 and look forward to our study findings in advanced CRC patients."

For more information on the Phase 1/2 clinical study in patients with unresectable locally advanced or metastatic CRC, refer to Clinicaltrials.gov identifier NCT05167448.

About ES104

ES104 is a bispecific antibody that simultaneously blocks Delta-like ligand 4/Notch (DLL4) and vascular endothelial growth factor A (VEGF-A) signaling pathways, which are critical to angiogenesis and tumor vascularization. Pre-clinical and early clinical data of ES104 show that blocking both pathways provides robust anti-tumor activity across several solid tumors, including colorectal, gastric, cholangiocarcinoma, pancreatic, and non-small cell lung cancer. Partial responses to ES104 as monotherapy have been observed in heavily pre-treated cancer patients, who were resistant to currently approved anti-VEGF therapies. ES104 has completed a Phase 1 monotherapy dose-escalation and expansion study (NCT03292783). Phase 1b and Phase 2 clinical studies (NCT04492033) in combination with chemotherapy are ongoing. Elpiscience licensed ES104 greater China rights from Compass Therapeutics in January 2021 and is conducting Phase 1/2 study in China for treatment in patients with unresectable locally advanced or metastatic colorectal cancer.