On August 7, 2023 Innovent Biologics, Inc. (Innovent) (HKEX: 01801), a world-class biopharmaceutical company that develops, manufactures and commercializes high-quality medicines for the treatment of oncology, metabolic, autoimmune, ophthalmology and other major diseases, reported that the preclinical results of IBI363 were published in Nature Cancer (IF=22.7). The publication entitled, "IL-2Rα-biased agonist enhances antitumor immunity by invigorating tumor-infiltrating CD25+CD8+ T cells" (Press release, Innovent Biologics, AUG 7, 2023, View Source [SID1234633889]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

Interleukin 2 (Interleukin-2, IL-2) is the first cytokine to be discovered and identified as playing a pivotal role in T-cell growth and expansion. Aldesleukin (IL-2) was approved by U.S. Food and Drug Administration for metastatic renal cell carcinoma and metastatic melanoma in the early 1990s, but it has not been widely used in clinic due to poor selectivity, narrow therapeutic window, and side effects. As a bi-functional cytokine, IL-2 can not only activate CD4+ regulatory T cells (Treg) via interaction with IL-2 receptor αβγ to suppress the immune system, but also stimulate CD8+ T cells and natural killer cells via its interaction with IL-2 receptor βγ to exert its anti-tumor effects. Most developers use the approach of eliminating IL-2 and IL-2 receptor α (IL-2Rα) as a strategy to reduce Treg activation while maximizing the anti-tumor effect of IL-2. However, these "not-α" IL-2 muteins performed poorly in clinical studies. The published manuscript describes the mechanism underlying this discrepancy. The major observations include:

In comparison with "not-α" IL-2, α-biased IL-2 which retains intact IL-2Rα (CD25) binding showed superior anti-tumor efficacy and lower toxicity in multiple murine tumor models.
In tumor, α-biased IL-2 can more effectively activate tumor-specific T cells (TSTs) because TSTs highly express CD25, which increases their interactions with α-biased IL-2. In contrast, "not-α" IL-2 is prone to expand CD25 negative bystander T cells, and this limits its anti-tumor efficacy. In the periphery, "not-α" IL-2 can significantly expand peripheral T cells, while α-biased IL2 preferentially expand peripheral Treg to restrain systemic toxicity.
Intratumoral CD25+PD-1+CD8+ T cells exert more potent polyfunctionalities, including secreting effector molecules such as IL-2, IFN-γ, TNF-α and GZMB, than CD25-PD-1+CD8+ and CD25-PD-1+CD8- T cells. CD25-blocking or IL-2-neutralizing antibodies can limit the activation of TSTs and negatively affect the anti-tumor effects of PD-1 blockade.
The corresponding author, Dr. Kaijie He of Innovent Biologics stated, "We are very pleased that the results of this study are published and highlighted in the current issue of Nature Cancer. IL-2 is one of the most important cytokines in immune-oncology, but the mechanism of action underlying its potent antitumor activity is still elusive. In this study, we propose a previously underappreciated function of CD25 in regulating IL-2 autocrine signaling in TST cells to exert their antitumor functions, and challenge the "IL-2 dogma" that has dominated the whole field in the past decades, suggesting a new approach to designing safer and more effective IL-2 drugs. At the same time, this study also proposes to use "IL-2 signature" as a novel biomarker to predict the clinical benefits of anti-PD-1 antibody in cancer patients, and provides scientific rationales of combining IL-2 and PD-1 antibody in individuals who do not respond to PD-1 blockade. Based on the findings of this study, we designed IBI363, a PD-1/IL-2 bispecific antibody fusion protein, to expand and re-invigorate the TST cells in the cold tumors and overcome resistance to PD-1 antibodies in certain populations. At present, IBI363 is in clinical Phase 1 studies to evaluate the safety and preliminary antitumor efficacy in cancer patients who have failed or are not suitable for anti-PD-1 treatment. "

IBI363 is a potential First-in-Class candidate drug independently developed by Innovent. Its active ingredient is PD-1/IL-2 bispecific antibody fusion protein. The IL-2 arm of IBI363 has been engineered to maximize efficacy and reduce toxicity, whereas the PD-1 binding arm achieves PD-1 blockade and selective IL-2 delivery. Therefore, IBI363 has both functions of simultaneously blocking PD-1/PD-L1 pathway and activating IL-2 pathway, allowing more precise and efficient targeting and activation of tumor specific T cells. IBI363 not only showed promising anti-tumor activity in a variety of tumor-bearing pharmacological models, but also exhibited prominent antitumor efficacy in PD-1 resistant and metastatic models; meanwhile, IBI363 demonstrated a good safety profile in preclinical models. Currently, Phase 1 studies of IBI363 are conducted in China and Australia to assess the safety, tolerability, and preliminary efficacy in subjects with advanced solid tumors or lymphoma.

On August 7, 2023 Merus N.V. (Nasdaq: MRUS) (Merus, the Company, we, or our), a clinical-stage oncology company developing innovative, full-length multispecific antibodies (Biclonics and Triclonics), reported financial results for the second quarter and provided a business update (Press release, Merus, AUG 7, 2023, View Source [SID1234633888]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"Receiving Fast Track Designation is an important milestone for petosemtamab, which we believe further validates its potential to address the unmet need of patients with previously treated recurrent or metastatic head and neck cancer," said Bill Lundberg, M.D., President, Chief Executive Officer of Merus. "We also believe the robust clinical data observed in previously treated HNSCC support a phase 3 trial of petosemtamab monotherapy in this setting, which could potentially start in mid-2024. Additionally, we are encouraged by our progress to date with the combination of petosemtamab and Keytruda as potential front-line therapy in advanced HNSCC, and are evaluating a phase 3 trial in this setting as well."

Petosemtamab (MCLA-158: EGFR x LGR5 Biclonics): Solid Tumors
Granted Fast Track Designation (FTD) for the treatment of patients with recurrent or metastatic head & neck squamous cell carcinoma (HNSCC), enrollment continues in dose expansion in the phase 1/2 trial with petosemtamab monotherapy in previously treated HNSCC, as well as in combination with Keytruda (pembrolizumab) as front-line therapy.

Petosemtamab is in clinical development in the expansion part of a phase 1/2 open-label, multicenter trial evaluating petosemtamab monotherapy in patients with advanced solid tumors, including previously treated (recurrent or metastatic) HNSCC. Enrollment is also ongoing in a cohort investigating petosemtamab in combination with Keytruda in patients with untreated HNSCC to evaluate the safety and clinical activity in this population. Merus plans to report initial interim clinical data from this cohort in the first half of 2024.

Initiation of potential registration-enabling trial

Merus is enrolling up to a total of approximately 40 patients in previously treated (2L/3L) HNSCC with petosemtamab monotherapy at the 1100 or 1500 mg dose levels to confirm a suitable dose for future randomized trials. Based on these data and additional information and analyses, Merus anticipates potentially initiating a randomized phase 3 trial of petosemtamab monotherapy, or investigators’ choice of single agent chemotherapy or cetuximab in 2L/3L HNSCC. Merus anticipates such a trial could potentially start in mid-2024. Merus believes a randomized registration trial in HNSCC with an overall response rate (ORR) endpoint could potentially support accelerated approval and the overall survival (OS) results from the same study could potentially verify its clinical benefit to support regular approval.

Merus is also evaluating a phase 3 trial investigating petosemtamab with Keytruda as a potential front-line therapy for advanced HNSCC expressing PD-L1 (CPS > 1), pending analysis of additional data on the tolerability and safety of the drug combination.

Fast Track Designation

The U.S. Food & Drug Administration (FDA) has granted FTD for petosemtamab for the treatment of patients with recurrent or metastatic HNSCC whose disease has progressed following treatment with platinum-based chemotherapy and an anti-programmed cell death protein 1 (anti-PD-1) antibody.

FTD is designed to facilitate the development and expedite the review of drugs to treat serious conditions and fill unmet medical needs.

Interim data from AACR (Free AACR Whitepaper)

In April, Merus provided an interim clinical update at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2023. As of a February 1, 2023 data cutoff date, 49 previously treated HNSCC patients were treated with petosemtamab at the initial recommended phase 2 dose of 1500 mg intravenously every two weeks. The ORR, in 43 evaluable patients, was 37.2% by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. per investigator assessment. Median duration of response was 6.0 months and median progression free survival was 5.3 months. 63% of responders had an ongoing response at the data cutoff date. Median OS was 11.5 months. Petosemtamab continued to demonstrate a manageable safety profile.

Zenocutuzumab (Zeno or MCLA-128: HER2 x HER3 Biclonics): NRG1 fusion (NRG1+) cancer and other solid tumors
Granted Breakthrough Therapy Designation (BTD) for both NRG1+ non-small cell lung cancer (NSCLC) and NRG1+ pancreatic cancer; enrollment continues in the eNRGy trial of Zeno monotherapy in NRG1+ cancer and a phase 2 trial of Zeno in combination with androgen deprivation therapy (ADT) in castration resistant prostate cancer (CRPC); as well as in combination with afatinib in NRG1+ non-small cell lung cancer (NSCLC)

The FDA has granted BTD to Zeno for the treatment of patients with advanced unresectable or metastatic NRG1+ pancreatic cancer following progression with prior systemic therapy or who have no satisfactory alternative treatment options. Additionally, the FDA has granted BTD to Zeno for the treatment of patients with advanced unresectable or metastatic NRG1+ NSCLC, following progression with prior systemic therapy. Zeno is being investigated in the phase 1/2 eNRGy trial and Early Access Program (EAP) which are assessing the safety and anti-tumor activity of Zeno monotherapy in NRG1+ cancer (Phase 1/2: NCT02912949, EAP: NCT04100694).

As of June 2023, more than 175 patients with NRG1+ cancer have been treated with Zeno monotherapy. The company continues to work with the FDA and is focused on accumulating data to support a potential Biologics License Application.

Merus believes that obtaining a commercialization partnership agreement will be an essential step in bringing Zeno to patients with NRG1+ cancer, if approved.

Merus plans to present a clinical update on Zeno in NRG1+ cancer at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) 2023 taking place in Madrid, Spain October 20-24, 2023. The presentations will consist of a mini-oral lecture titled: Durable efficacy of zenocutuzumab, a HER2 x HER3 bispecific antibody, in advanced NRG1 fusion-positive (NRG1+) non-small cell lung cancer (NSCLC) and a poster presentation titled: Durable efficacy of zenocutuzumab, a HER2 x HER3 bispecific antibody, in advanced NRG1 fusion-positive (NRG1+) pancreatic ductal adenocarcinoma (PDAC).

Further, Merus is evaluating Zeno in combination with an ADT (enzalutamide or abiraterone) in men with CRPC, irrespective of NRG1+ status. Merus plans to provide initial clinical data on Zeno in CRPC in the second half of 2023.

Merus is also evaluating Zeno in combination with afatinib in patients with NRG1+ NSCLC.

MCLA-129 (EGFR x c-MET Biclonics): Solid Tumors
Enrollment continues in the expansion cohorts in the phase 1/2 trial; clinical update planned for 2H23

MCLA-129 is in clinical development in a phase 1/2, open-label clinical trial evaluating MCLA-129 monotherapy in patients with EGFR ex20 NSCLC, MET ex14 NSCLC, and in HNSCC, as well as MCLA-129 in combination with Tagrisso, a third generation EGFR TKI, in patients with treatment-naïve EGFR mutant (m) NSCLC and in patients with EGFRm NSCLC that have progressed on Tagrisso.

In April, Merus provided a pre-clinical presentation of MCLA-129 in comparison with amivantamab at the AACR (Free AACR Whitepaper) Annual Meeting 2023. The Company plans to provide an initial clinical data update from the expansion cohorts, and a further clinical development strategy update in the second half of 2023.

MCLA-129 is subject to a collaboration and license agreement with Betta Pharmaceuticals Co. Ltd. (Betta), which permits Betta to develop MCLA-129 and potentially commercialize exclusively in China, while Merus retains global rights outside of China.

In July, the National Medical Products Administration in China approved the investigational new drug application permitting Betta to investigate the combination of MCLA-129 and befotertinib, a third generation EGFR tyrosine kinase inhibitor, in adult patients in China that have locally advanced or metastatic NSCLC, with an EGFR Exon 19 deletion mutation or Exon 21 (L858R) substitution mutation.

MCLA-145 (CD137 x PD-L1 Biclonics): Solid Tumors
Enrollment continues in the phase 1 trial, including in combination with Keytruda (pembrolizumab), a PD-1 inhibitor

MCLA-145 is in clinical development in a global, phase 1, open-label, clinical trial evaluating MCLA-145 in patients with solid tumors. The trial is in the dose expansion phase evaluating the combination of MCLA-145 with Keytruda, with enrollment ongoing.

Collaborations

Incyte Corporation
Since 2017, Merus has been working with Incyte Corporation (Incyte) under a global collaboration and license agreement focused on the research, discovery and development of bispecific antibodies utilizing Merus’ proprietary Biclonics technology platform. The agreement grants Incyte certain exclusive rights for up to ten bispecific and monospecific antibody programs. The collaboration is progressing, with multiple programs in various stages of preclinical and clinical development. For each program under the collaboration, Merus receives reimbursement for research activities and is eligible to receive potential development, regulatory and commercial milestones and sales royalties for any products, if approved. Further, Incyte announced, in 2023, that INCA33890, a novel TGFBr2xPD1 bispecific antibody developed through the collaboration is currently being evaluated in clinical studies. In July 2023, Merus achieved a milestone and expects a payment of $2.5 million related to the advancement of this program in the third quarter of 2023.

Loxo Oncology at Lilly
In January 2021, Merus and Loxo Oncology at Lilly, a research and development group of Eli Lilly and Company (Lilly), announced a research collaboration and exclusive license agreement to develop up to three CD3-engaging T-cell re-directing bispecific antibody therapies utilizing Merus’ Biclonics platform and proprietary CD3 panel along with the scientific and rational drug design expertise of Loxo Oncology at Lilly. The collaboration is progressing with multiple active research programs underway.

Cash Runway, existing cash, cash equivalents and marketable securities expected to fund Merus’ operations into 2026
As of June 30, 2023, Merus had $311.5 million cash, cash equivalents and marketable securities. Based on the Company’s current operating plan, the existing cash, cash equivalents and marketable securities are expected to fund Merus’ operations into 2026.

Second Quarter 2023 Financial Results

We ended the second quarter with cash, cash equivalents and marketable securities of $311.5 million compared to $326.7 million at December 31, 2022.

Collaboration revenue for the three months ended June 30, 2023 decreased by $2.2 million as compared to the three months ended June 30, 2022, primarily as a result of decreases in reimbursement revenue of $0.5 million, milestone revenue of $1.0 million and amortization of deferred revenue of $0.7 million.

Research and development expense for the three months ended June 30, 2023 decreased by $2.8 million as compared to the three months ended June 30, 2022, primarily as a result of decreases in external clinical services and drug manufacturing costs, including costs to fulfill our obligations under our collaboration agreements, related to our programs of $3.8 million and a decrease in facilities costs of $0.5 million, partially offset by an increase in personnel related expenses including stock-based compensation of $1.5 million due to an increase in employee headcount.

General and administrative expense for the three months ended June 30, 2023 increased by $3.4 million as compared to the three months ended June 30, 2022, primarily as a result of increases in facilities costs including depreciation of $1.6 million, consulting costs of $1.2 million, IP and license costs of $0.4 million, and travel expenses of $0.4 million, partially offset by a decrease in finance and human resources costs of $0.2 million.

Collaboration revenue for the six months ended June 30, 2023 decreased by $0.3 million as compared to the six months ended June 30, 2022, primarily as a result of a decrease in reimbursement revenue of $0.9 million, decrease of amortization of deferred revenue of $0.9 million partially offset by an increase in milestone revenue of $1.5 million.

Research and development expense for the six months ended June 30, 2023 increased by $5.1 million as compared to the six months ended June 30, 2022, primarily as a result of increases in personnel related expenses including stock-based compensation of $3.7 million, external clinical services and drug manufacturing costs, including costs to fulfill our obligations under our collaboration agreements, related to our programs of $1.6 million, consulting expenses of $0.6 million, and consumables expenses of $0.3 million and travel costs of $0.2 million, partially offset by decreases in facilities costs of $0.8 million and partner expenses of $0.5 million. General and administrative expense for the six months ended June 30, 2023 increased by $7.0 million as compared to the six months ended June 30, 2022, primarily as a result of increases in consulting costs of $3.6 million, facilities costs including depreciation of $2.8 million, travel costs of $0.6 million, personnel related expenses including stock-based compensation of $0.5 million due to an increase in employee headcount, and IP and license costs of $0.3 million, partially offset by decreases in finance and human resources costs of $0.8 million.

Other income (loss), net consists of interest earned and fees paid on our cash and cash equivalents held on account, accretion of investment earnings and net foreign exchange (losses) gains on our foreign denominated cash, cash equivalents and marketable securities. Other gains or losses relate to the issuance and settlement of financial instruments.

On August 7, 2023 Cardiff Oncology, Inc. (Nasdaq: CRDF), a clinical-stage biotechnology company leveraging PLK1 inhibition, a well-validated oncology drug target, to develop novel therapies across a range of cancers, reported plans to advance the company’s lead program to the first-line setting of metastatic colorectal cancer (mCRC) and conduct its new CRDF-004 trial with study execution support from Pfizer Ignite, a new end-to-end service for biotech companies (Press release, Cardiff Oncology, AUG 7, 2023, View Source [SID1234633887]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"Our advance to the first-line mCRC setting is the result of a comprehensive data-driven review coupled with the agreement and support of the FDA. Ultimately, this decision moves Cardiff Oncology into a stronger position to realize the promise of onvansertib for the benefit of patients and all of our stakeholders," said Mark Erlander, Ph.D., Chief Executive Officer of Cardiff Oncology. "We are delighted to expand our relationship with Pfizer and conduct this new first-line trial beginning this fall through Pfizer Ignite, leveraging its clinical execution capabilities and expertise."

The company estimates that there are 48,000 new patients in the U.S. annually in the first-line RAS-mutated mCRC setting for whom there are no ongoing clinical trials and no new treatments approved in the past 20 years.

Dr. Erlander continued: "Key to today’s decision has been our discovery of a novel mechanism of action by which onvansertib inhibits angiogenesis by turning off a ‘survival switch’ for tumorigenesis. This has helped us understand onvansertib’s interaction with bevacizumab, and the compelling clinical results we observed in our Phase 1b/2 second-line KRAS-mutated mCRC trial."

The clinical activities of the company’s new CRDF-004 trial in first-line RAS-mutated mCRC will be conducted with support from Pfizer Ignite. This expands the relationship established in November 2021 when Pfizer made an equity investment in Cardiff Oncology and nominated Adam Schayowitz, Ph.D., Vice President & Medicine Team Group Lead for Breast Cancer, Colorectal Cancer and Melanoma, Pfizer Global Product Development as a Scientific Advisory Board member.

Pfizer Ignite is a new end-to-end service for biotech companies with high potential science that leverages Pfizer Inc.’s significant R&D capabilities, scale and expertise to accelerate the development of breakthrough therapies.

Cardiff Oncology will maintain full economic ownership and control of onvansertib.

"We believe onvansertib, by inhibiting PLK1, has the potential to play a meaningful role in the treatment of several types of cancer, including the lead program in RAS-mutated mCRC," said Dr. Schayowitz. "We believe that by combining Pfizer’s clinical development capabilities and expertise, with onvansertib’s promising novel clinical findings, we have an opportunity to accelerate the advancement of this program for the benefit of the many patients in the RAS-mutated mCRC setting."

Cardiff Oncology’s new lead program in first-line RAS-mutated mCRC will consist of two trials that will be conducted sequentially. The first trial will be CRDF-004, a Phase 2 randomized trial generating preliminary safety and efficacy data and evaluating two different doses of onvansertib to confirm an optimal dose. Onvansertib will be added to standard-of-care consisting of FOLFIRI plus bevacizumab, or FOLFOX plus bevacizumab. A total of 90 patients will be randomized in a 1:1:1 ratio to either 20mg of onvansertib plus standard-of-care, 30mg of onvansertib plus standard-of-care, or standard-of-care alone. Interim topline results from this trial are expected in mid-2024.

Contingent upon the results of CRDF-004, Cardiff Oncology will initiate a Phase 3, randomized trial with registrational intent. The FDA has agreed that a seamless trial with objective response rate (ORR) at an interim point is an acceptable endpoint to pursue accelerated approval, with progression-free survival (PFS) and trend in overall survival being the endpoints for full approval.

"The stand-out results from our Phase 1b/2 second-line mCRC trial of onvansertib were observed in a well-defined subset of patients, namely those who had not previously been treated with bevacizumab in the first-line setting," said Fairooz Kabbinavar, MD, Chief Medical Officer of Cardiff Oncology. "Bev naïve patients in our Phase 1b/2 trial who received FOLFIRI, bevacizumab and onvansertib had a remarkable 73% ORR and 15-month mPFS, comparing favorably against historical controls that report an ORR of approximately 25% with a 7 to 8-month mPFS. Such high levels of efficacy have not been previously observed in 2nd line mCRC. The clinical and preclinical data we are reporting today confirm our initial finding, and based on highly encouraging interactions with the FDA and Pfizer, we are moving into first-line RAS-mutated mCRC where we believe enrollment should occur more quickly given the significantly larger number of first-line patients versus second-line."

Consistent with the strategic decision to focus on first-line RAS-mutated mCRC, Cardiff Oncology will discontinue enrollment in its ONSEMBLE second-line trial to focus resources on its new lead first-line program. This decision is driven by the fact that both trials essentially test the same clinical hypothesis, the importance of deploying the Company’s capital efficiently, and the FDA’s suggestion that Cardiff Oncology consider focusing on the first-line RAS-mutated mCRC setting.

All other Cardiff Oncology programs remain unaffected by this decision.

Conference Call and Webcast

Cardiff Oncology will host a corresponding conference call and live webcast at 5:00 p.m. ET/2:00 p.m. PT on August 7, 2023. Individuals interested in listening to the live conference call may do so by using the webcast link in the "Investors" section of the company’s website at www.cardiffoncology.com. A webcast replay will be available in the investor relations section on the company’s website for 30 days following the completion of the call.

On August 7, 2023 Zai Lab Limited (NASDAQ: ZLAB; HKEX: 9688) reported financial results for the second quarter of 2023, along with recent product highlights and corporate updates (Press release, Zai Laboratory, AUG 7, 2023, View Source [SID1234633886]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"In the second quarter of 2023, we continued to successfully execute across our business. Our commercial products continued to deliver strong growth, with net product revenues growing 53% on a constant currency basis, and we made important progress for several late-stage and early development programs within our pipeline," said Dr. Samantha Du, Founder, Chairperson, and Chief Executive Officer of Zai Lab. "Most importantly, we gained NMPA approval of VYVGART, a first-in-class therapy that has the potential to significantly transform the lives of patients living with gMG in China, and we were able to achieve this monumental milestone on June 30th, which makes us eligible for NRDL listing in 2024. More recently, the positive data for efgartigimod in CIDP supports our confidence in its blockbuster potential across multiple indications."

"Looking ahead, Zai Lab has the potential for significant revenue growth and margin expansion over the next five years," said Josh Smiley, President and Chief Operating Officer of Zai Lab. "As highlighted at our 2023 Investor Day, we expect to have over 15 commercial-stage products, and at least one IND per year for global best-in-class/first-in-class assets, by the end of 2028. We expect our robust portfolio of assets to drive a revenue compound annual growth rate of over 50% from 2023 to 2028. As we launch new products and indications, we will continue to be prudent and capital efficient, prioritizing our R&D efforts and driving increased productivity across the organization. We expect that this discipline, along with our expected revenue growth, will allow us to reach corporate profitability by the end of 2025." Mr. Smiley concluded.

Recent Product Highlights and Corporate Updates

Zai Lab has established a differentiated portfolio and pipeline of assets, including 13 in late-stage development. We have had a number of exciting developments with respect to our products and product candidates, including the following updates since our last earnings release:

Commercial Products

We continued to increase sales for each of our commercial products in the second quarter of 2023, compared to the same period in 2022, driven by increased access for ZEJULA, QINLOCK, and NUZYRA as a result of their inclusion in the National Reimbursement Drug List (NRDL) and for Optune as a result of increased supplemental insurance plan coverage.

We also received the following regulatory approvals for our commercial products during the second quarter of 2023:

•VYVGART: In June 2023, we received approval from the NMPA for the BLA for VYVGART (efgartigimod alfa injection), a first-in-class FcRn antagonist, as an add on standard therapy for the treatment of adult patients with gMG who are anti-acetylcholine receptor (AChR) antibody positive. We expect to commercially launch VYVGART in mainland China later this year.

•Optune: In May 2023, the Taiwan Food and Drug Administration approved the Marketing Authorization Application (MAA) of Optune for the treatment of patients with glioblastoma multiforme (GBM).
1

Key Product Candidate Developments

We continued to advance our product candidates through our research and development and commercial operations, including the following developments with respect to our clinical trials and regulatory approvals:

Oncology

•ZEJULA (niraparib, PARP): In July 2023, data from the Phase 3 PRIME study were published in JAMA Oncology, supporting the utility of ZEJULA as a maintenance therapy in a broad population of Chinese patients with newly diagnosed advanced ovarian cancer and demonstrating that an individual starting dose (ISD) of 200 or 300mg based on baseline bodyweight and platelet count can bring significant benefit to patients with an improved safety and tolerability profile of ZEJULA compared to a fixed 300mg starting dose. These data demonstrate that maintenance treatment with ZEJULA can significantly prolong progression-free survival versus placebo and can reduce the risk of disease progression or death by 55% with newly diagnosed advanced ovarian cancer.

•Tumor Treating Fields (TTFields or Optune):

–Pancreatic Cancer: In July 2023, Zai Lab partner NovoCure Limited (NovoCure) announced a favorable Independent Data Monitoring Committee recommendation to continue the Phase 3 PANOVA-3 clinical trial of TTFields therapy in pancreatic cancer. Pre-specified interim analysis concluded that the fully enrolled PANOVA-3 clinical trial should proceed to final analysis as planned. Zai Lab participated in the Greater China portion of the study.

–NSCLC: In June 2023, Zai Lab and NovoCure announced the LUNAR Phase 3 clinical trial met the primary endpoint, demonstrating a statistically significant and clinically meaningful extension in overall survival for patients with metastatic NSCLC after platinum-based therapies. Zai Lab participated in the Greater China portion of the study.
•Tumor Treating Fields therapy together with standard of care provided a statistically significant and clinically meaningful 3-month improvement in median overall survival versus standard of care with no added systemic toxicities; and
•Tumor Treating Fields therapy together with immune checkpoint inhibitors resulted in an unprecedented 8-month improvement in median overall survival.

•KRAZATI (adagrasib, KRASG12C):

–In July 2023, Zai Lab completed enrollment in China for the global Phase 3 KRYSTAL-10 trial of adagrasib in combination with cetuximab vs. chemotherapy in patients with previously treated advanced KRASG12C-mutated colorectal cancer.

–In June 2023, Zai Lab completed enrollment in China for the global Phase 2 KRYSTAL-7 trial of adagrasib in combination with pembrolizumab as first-line treatment for patients with advanced KRASG12C-mutated NSCLC.

•Repotrectinib (ROS1/TRK): In June 2023, Zai Lab announced that the National Medical Products Administration (NMPA) in China has accepted its New Drug Application (NDA) for repotrectinib for the treatment of adult patients with locally advanced or metastatic ROS1-positive NSCLC, after granting priority review in May 2023. In May 2023, Zai Lab partner Bristol Myers Squibb (BMS) announced that the NDA for repotrectinib was accepted for priority review by the FDA for the same indication, with a Prescription Drug User Fee Act (PDUFA) date of November 27, 2023.

•Bemarituzumab (FGFR2b): In July 2023, Zai Lab enrolled the first patient in the mainland China portion of the global Phase 3 FORTITUDE-101 study of bemarituzumab plus chemotherapy, versus placebo plus chemotherapy, in first-line gastric cancer with FGFR2b overexpression.

Autoimmune Disorders, Infectious Diseases and Neuroscience

•VYVGART (efgartigimod, FcRn):

–gMG: In June 2023, argenx BV (argenx) announced that the FDA approved VYVGART Hytrulo (efgartigimod alfa and hyaluronidase-qvfc) injection for subcutaneous use in gMG. In July 2023, the NMPA accepted Zai Lab’s BLA for efgartigimod alfa injection (subcutaneous injection) for the treatment of adult patients with gMG.

–CIDP: In July 2023, Zai Lab and argenx announced positive topline results from the global registrational ADHERE study evaluating VYVGART Hytrulo in adults with CIDP. Zai Lab participated in the Greater China portion of the study. Highlights of the results include:
–Primary endpoint met (p=0.000039); VYVGART Hytrulo demonstrated a 61% reduction (HR: 0.39 95% CI: 0.25; 0.61) in the risk of relapse versus placebo;
–67% of patients in open-label Stage A demonstrated evidence of clinical improvement (ECI), indicating that IgG autoantibodies play a significant role in the underlying biology of CIDP; and
–Safety and tolerability profile was consistent with previous clinical trials and the confirmed safety profile of VYVGART.

2

–Bullous pemphigoid (BP): In May 2023, Zai Lab enrolled the first patient in China in the global Phase 2/3 BALLAD study of SC efgartigimod in adult patients with BP.

•XACDURO (SUL-DUR, Asia Pacific rights): In May 2023, Zai Lab partner Entasis Therapeutics, Inc. (Entasis), a wholly owned subsidiary of Innoviva, Inc., announced that the FDA approved XACDURO for the treatment of adults with hospital-acquired bacterial pneumonia and ventilator-associated bacterial pneumonia (HABP/VABP) caused by susceptible strains of Acinetobacter baumannii-calcoaceticus complex (Acinetobacter). The Company’s NDA is under review at the NMPA with priority review status in China.

•KarXT (xanomeline-trospium, M1/M4-preferring muscarinic agonist): In June 2023, Zai Lab enrolled the first patient in the registrational bridging study in mainland China for KarXT for the treatment of patients with schizophrenia.

Corporate Updates

•Organizational update: In July 2023, Zai Lab promoted Yajing Chen to Chief Financial Officer (CFO), effective July 7, 2023. Dr. Chen previously served as Zai Lab’s Senior Vice President and Deputy CFO, helping to oversee finance, planning and forecasting, accounting, tax, treasury, and procurement matters since joining the Company in September 2021. She is a seasoned finance executive with more than 20 years of experience in the life sciences industry as well as a Ph.D. trained scientist. She joined the Company from AstraZeneca where she held various roles of increasing responsibility from 2006 to 2021, including Chief Financial Officer for the U.S. Oncology Business Unit from 2019 to 2021 and Finance Controller of the Global Oncology Business Unit from 2016 to 2019. Her scientific background combined with her significant executive management experience, finance expertise at leading global companies, and business acumen provide a unique and valuable perspective to the Company and will help drive our next phase of growth. Dr. Chen succeeds Billy Cho, who stepped down from his role and left the Company on July 7, 2023.

•2023 Investor Day: Zai Lab hosted an Investor Day in New York on Tuesday, June 20, 2023.

–Zai Lab highlighted its 5-year growth strategy, including the following goals by the end of 2028:

•Over 15 commercial-stage products in 2028 (versus 5 today)

•Over 8 clinical-stage global-right products in 2028 with at least one Investigational New Drug application (IND) per year (versus 3 today)

•Revenue compound annual growth rate (CAGR) of >50% from 2023 to 2028

•Significant revenue growth and expanding operating margins to lead to corporate profitability by the end of 2025

–In addition, Zai Lab spotlighted multiple key programs with over $1 billion peak sales potential, starting with efgartigimod.

Anticipated Major Milestones in 2023

Oncology

Tumor Treating Fields or TTFields

•Zai Lab partner NovoCure to provide a topline data readout from the global pivotal INNOVATE-3 clinical study testing the efficacy of TTFields together with paclitaxel in platinum-resistant ovarian cancer.

KRAZATI (adagrasib, KRASG12C)

•Zai Lab partner Mirati Therapeutics, Inc. (Mirati) to provide a clinical data update for the global Phase 2 KRYSTAL-7 study of adagrasib in combination with pembrolizumab in first-line KRASG12C-mutated NSCLC. Zai Lab is participating in the study in Greater China.

•Mirati to provide an update on its multi-pronged development approach in first-line KRASG12C-mutated NSCLC.

•Mirati to submit a supplemental New Drug Application (sNDA) for Accelerated Approval to the FDA in third-line+ KRASG12C-mutated advanced colorectal cancer (CRC).

Odronextamab (CD20xCD3)

•Zai Lab partner Regeneron Pharmaceuticals, Inc. (Regeneron) to initiate confirmatory studies in follicular lymphoma (FL) and diffuse large B-cell lymphoma (DLBCL) including in earlier lines.

•Regeneron expects to receive BLA and Marketing Authorisation Application (MAA) acceptance in relapsed/refractory FL and DLBCL.
3

MARGENZA (margetuximab, HER2)

•Potential NMPA approval of the NDA for margetuximab in third-line+ metastatic HER2+ breast cancer.

Autoimmune Disorders, Infectious Disease and Neuroscience

VYVGART (efgartigimod, FcRn)

•Zai Lab partner argenx to report topline data from the registrational Phase 3 ADDRESS trial of SC efgartigimod in pemphigus and the registrational Phase 3 ADVANCE-SC trial of SC efgartigimod in immune thrombocytopenia (ITP) in the fourth quarter of 2023. Zai Lab participated in both studies in Greater China.

•argenx to initiate a registrational study of efgartigimod in thyroid eye disease (TED) in the fourth quarter of 2023.

KarXT (xanomeline-trospium, M1/M4-preferring muscarinic agonist)

•Zai Lab partner Karuna to submit an NDA to the FDA for KarXT for the treatment of patients with schizophrenia in the third quarter of 2023.

•Karuna to initiate the Phase 3 ADEPT-2 and ADEPT-3 trials in Alzheimer’s disease psychosis. Zai Lab plans to participate in these studies in Greater China.

Second Quarter 2023 Financial Results

•Product revenues were $68.9 million for the second quarter of 2023, compared to $47.6 million for the same period in 2022, representing 45% y-o-y growth; y-o-y growth was 53% at constant exchange rate. The increase in product revenues was primarily due to increased sales volumes and decreased negative effects from the COVID-19 pandemic. The product revenues in the second quarter of 2023, compared to the same period in 2022, included:

–$43.0 million for ZEJULA, which increased 26% from $34.1 million; and
–$13.7 million for Optune, which increased 18% from $11.6 million; and
–$7.5 million for QINLOCK, which increased from $0.6 million; and
–$4.6 million for NUZYRA, which increased from $1.3 million.

•Research and Development (R&D) expenses were $76.7 million for the second quarter of 2023, compared to $66.1 million for the same period in 2022. The increase in R&D expenses was primarily due to increased research activities and clinical pipeline advancement.

•Selling, General and Administrative expenses were $67.9 million for the second quarter of 2023, compared to $63.4 million for the same period in 2022. The increase was primarily due to higher general selling expenses to support new product launches.

•Net loss was $120.9 million for the second quarter of 2023, or a loss per ordinary share attributable to common stockholders of $0.13, compared to a net loss of $137.9 million for the same period in 2022, or a loss per ordinary share of $0.14. The decrease in net loss was primarily due to product revenue growing faster than net operating expenses.

•Cash and cash equivalents, short-term investments and restricted cash totaled $876.4 million as of June 30, 2023, compared to $931.4 million as of March 31, 2023.

Conference Call and Webcast Information

Zai Lab will host a live conference call and webcast tomorrow, August 8, 2023, at 8:00 a.m. ET. Listeners may access the live webcast by visiting the Company’s website at View Source Participants must register in advance of the conference call.

Details are as follows:

Registration Link: https://register.vevent.com/register/BIb7d99f107c3347f29e117b2b7bc47034

All participants must use the link provided above to complete the online registration process in advance of the conference call. Dial-in details will be in the confirmation email which the participant will receive upon registering.

A replay will be available shortly after the call and can be accessed by visiting the Company’s website.

On August 7, 2023 Vincerx Pharma, Inc. (Nasdaq: VINC), a biopharmaceutical company aspiring to address the unmet medical needs of patients with cancer through paradigm-shifting therapeutics, reported financial results for the second quarter ended June 30, 2023 and provided a corporate update (Press release, Vincerx Pharma, AUG 7, 2023, View Source [SID1234633885]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"I am excited to report that the Investigational New Drug (IND) application for our first antibody-drug conjugate (ADC), VIP943, was filed and is under review by the U.S. Food and Drug Administration (FDA)," said Ahmed Hamdy, M.D., Chief Executive Officer of Vincerx. "We believe that our next-generation ADC technology represents a significant step forward in the treatment of cancer by potentially overcoming the safety and efficacy challenges associated with many ADCs. Our unique combination of internalizing antibodies, selective and stable linkers, novel payloads, and exclusive CellTrapper technology allows for greater intracellular accumulation of the payload, potentially leading to higher efficacy while limiting unwanted side effects. We currently expect to dose our first patient with VIP943 in the fourth quarter."

"We also continue enrolling patients in our Phase 1 dose escalation study for VIP236, our first-in-class small molecule drug-conjugate (SMDC). VIP236 is designed to deliver an optimized camptothecin payload to tumors expressing αvβ3, which is found in advanced and metastatic tumors. Encouragingly, VIP236 preclinical data shows enhanced efficacy—independent of HER2 status— in patient-derived xenograft (PDX) and cell line-derived gastric cancer models compared with the ADC ENHERTU. Given the first-in-class nature of this program, we are evaluating several dosing approaches and expect to provide preliminary results by late 2023 or early 2024."

"On the business development front, we are thrilled to welcome Mr. Steve Bloom as our new Chief Business Officer. With Steve on board, we believe we are positioned to accelerate our ongoing business development activities and capitalize on the burgeoning industry enthusiasm for bioconjugates."

"As we enter the latter half of the year, we are strategically focusing our resources on VIP943 and VIP236, along with exploring potential research and other collaborations that can bolster the advancement of these two lead programs, as well as leverage the strength of our next-generation modular bioconjugation platform," concluded Dr. Hamdy.

Second Quarter 2023 Corporate Highlights

VIP943, CD123-KSPi ADC: for Leukemias and Myelodysplastic Syndrome:

IND for VIP943 filed; anticipate enrolling the first patient in a Phase 1 dose escalation study in Q4 2023
Presented preclinical data at ASH (Free ASH Whitepaper) 2022 demonstrating superiority with significantly improved safety in monkeys and better efficacy in a mouse model of acute leukemia when compared with Mylotarg
VIP236, an αvβ3 Integrin Binder Linked to an optCPT Payload SMDC:

Phase 1 first-in-human dose-escalation study with VIP236 monotherapy ongoing (ClinicalTrials.gov NCT05712889)
Presented compelling preclinical data at AACR (Free AACR Whitepaper) 2023 demonstrating that VIP236 had potent and durable tumor growth inhibition in multiple mouse models for non-small cell lung cancer (NSCLC), colorectal carcinoma (CRC), triple negative breast cancer (TNBC), and gastric cancers
VIP924, CXCR5-KSPi ADC: for B-cell Malignancies:

Presented promising preclinical data at AACR (Free AACR Whitepaper) 2023 demonstrating significant tumor growth inhibition in a panel of lymphoma cell lines and cell line-derived and PDX lymphoma models
Pacing investment as we focus resources on lead programs (VIP236 and VIP943)
Additional Platform Updates

Presented preclinical data at AACR (Free AACR Whitepaper) 2023 on synthesis and characterization of novel SMDCs with different payloads, highlighting the breadth and potential of our SMDC platform
Enitociclib, Positive Transcription Elongation Factor b (P-TEFb)/CDK9 Inhibitor:

Focused on Phase 1 study with the National Institutes of Health (NIH) evaluating combination of enitociclib and venetoclax and prednisone (VVIP) in diffuse large B-cell lymphoma (DLBCL) and peripheral T Cell Lymphoma (PTCL); enrollment ongoing (ClinicalTrials.gov NTC05371054)
Additional combination studies will be determined based on further financing/partnering support
Proof-of-concept monotherapy efficacy has been generated in early-stage clinical studies:
Hematologic malignancies: 2 patients with double-hit DLBCL achieved complete metabolic responses after 10 cycles of treatment and remain in remission, off treatment, for >4 years; 1 patient with transformed follicular lymphoma remains on treatment for >13 months with a maximum 43% reduction in target lesions
Solid tumors: 13 patients achieved stable disease, including durable disease control, in patients with ovarian, pancreatic cancer, and salivary gland cancer
Strong preclinical evidence for additional indications (eg, multiple myeloma) and pediatric indications
Second Quarter 2023 Financial Results

Vincerx had approximately $27.4 million in cash, cash equivalents and marketable securities as of June 30, 2023, as compared to approximately $52.5 million as of December 31, 2022. Vincerx expects its burn rate to decrease as a result of completing Chemistry, Manufacturing, and Controls (CMC) activities and prioritizing resources toward advancing Phase 1 studies for VIP236 and VIP943, its lead programs. Based on its current business plans and assumptions, Vincerx believes its available capital will be sufficient to meet its operating requirements into late 2024.
Research and development (R&D) expenses for the three- and six-months ended June 30, 2023 were approximately $7.9 million and $18.5 million, as compared to approximately $13.7 million and $29.7 million for the same periods in 2022. The decrease for the three-months ended June 30, 2023 compared with the same period in 2022 is primarily the result of decreases in stock-based compensation expense of approximately $2.0 million, payroll related costs of approximately $0.9 million as a result of our headcount reduction in June 2022, clinical services of approximately $1.1 million, and third party research and preclinical work of approximately $1.1 million. The decrease for the six-months ended June 30, 2023 compared with the same period in 2022 is primarily the result of decreases in stock-based compensation expense of approximately $5.0 million, payroll related costs of approximately $2.1 million as a result of the headcount reduction, clinical services of approximately $1.8 million, and manufacturing services associated with our ADC program of approximately $1.4 million.

General and administrative (G&A) expenses for the three- and six-months ended June 30, 2023 were approximately $3.8 million and $8.3 million, as compared to approximately $4.7 million and $10.4 million for the same periods in 2022. These decreases are primarily due to declines in stock-based compensation expense of approximately $0.7 million and $1.8 million for the three- and six-months ended June 30, 2023, respectively.
For the second quarter ended June 30, 2023, Vincerx reported a net loss of approximately $11.2 million, or $0.52 per share. For the second quarter ended June 30, 2022, Vincerx reported a net loss of approximately $18.4 million, or $0.88 per share. For the six-months ended June 30, 2023, Vincerx reported a net loss of $25.5 million, or $1.20 per share, as compared to a net loss of $34.8 million, or $1.66 per share for the same period in 2022.