On November 7, 2023 Summit Therapeutics Inc. (NASDAQ: SMMT) ("Summit," "we," or the "Company") reported its financial results and provides an update on operational progress for the third quarter and nine months ended September 30, 2023 (Press release, Summit Therapeutics, NOV 7, 2023, View Source [SID1234637204]).

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Operational & Corporate Updates

Our operational progress with ivonescimab (SMT112), an innovative, potentially first-in-class bispecific antibody combining the effects of immunotherapy via a blockade of PD-1 with the anti-angiogenesis effects associated with blocking VEGF into a single molecule:
We are actively engaged in development activities for SMT112. In just over nine months since we closed our in-licensing transaction for ivonescimab, we have:
Held multiple meetings with the US Food & Drug Administration (FDA) regarding our planned Phase III clinical program and incorporated this feedback accordingly,
Begun our clinical development in non-small cell lung cancer (NSCLC) in the following proposed indications:
Ivonescimab combined with chemotherapy in patients with epidermal growth factor receptor (EGFR)-mutated, locally advanced or metastatic non-squamous NSCLC who have progressed after treatment with a third-generation EGFR tyrosine kinase inhibitor (TKI) ("HARMONi" trial),
Ivonescimab combined with chemotherapy in first-line metastatic squamous NSCLC patients ("HARMONi-3" trial),
Launched the Phase III HARMONi clinical trial in less than 4 months of acquiring the rights to ivonescimab; enrollment is expected to complete in the second half of 2024
Commenced patient enrollment in the second Phase III clinical study, HARMONi-3.
Recapping our Collaboration and License Agreement with Akeso Inc. (Akeso) for ivonescimab (SMT112):
On December 5, 2022, Summit and Akeso entered into a Collaboration and License Agreement for ivonescimab.
The Collaboration and License Agreement with Akeso closed on January 17, 2023 after going effective following customary waiting periods.
Summit received the rights to develop and commercialize ivonescimab (SMT112) in the United States, Canada, Europe, and Japan. Akeso retained development and commercialization rights for the rest of the world, including China.
In exchange for these rights, Summit committed to an upfront payment of $500 million, which was paid in two installments.
The first installment worth $300 million was paid in January in conjunction with the closing of the transaction. Of the $300 million paid to Akeso by Summit, Akeso opted, in accordance with the Collaboration and License Agreement, to receive 10 million shares in lieu of a cash payment of $25.1 million; the remaining $274.9 million was paid by Summit to Akeso in cash.
The second installment of $200 million was paid on March 6, 2023 in cash.
Going forward, Akeso will be eligible to receive regulatory and commercial milestones of up to $4.5 billion. In addition, Akeso will receive low double-digit royalties on net sales in the Summit territories.
In June 2023, promising Phase II data from AK112-201, a study of Chinese subjects conducted and analyzed by our partners, Akeso, was presented at the 2023 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting. In addition to encouraging data in multiple indications within NSCLC, a portion of the updated data presented at ASCO (Free ASCO Whitepaper) supports Summit’s HARMONi-3 clinical trial in first-line metastatic squamous NSCLC.
Over 950 patients have been treated with ivonescimab in clinical studies in China and Australia, with enrollment beginning recently in Summit’s license territories.
Akeso has a rich and diversified antibody drug pipeline with over 30 internally discovered drug candidates in various stages of development, including six bispecific antibodies. Akeso has taken part in over 80 clinical trials for 17 drug candidates, including 14 pivotal trials. Akeso has two drugs approved for oncology indications in China: a PD-1 inhibitor and a novel PD-1 / CTLA-4 bispecific antibody. Akeso has over 2,700 employees.
In the beginning of Q4, we announced that we have bolstered our leadership and clinical experience at Team Summit:
Manmeet S. Soni has joined the Company as our Chief Operating Officer. Mr. Soni has over 20 years of financial and operational leadership experience. He was President, Chief Operating Officer, & Chief Financial Officer at Reata Pharmaceuticals, Inc., which was sold to Biogen Inc. for $7.5 billion. Prior to Reata, Mr. Soni was the CFO at Alnylam Pharmaceuticals, Inc. and Ariad Pharmaceuticals, Inc., the latter of which was purchased by Takeda Pharmaceutical Co. Ltd. for $5.4 billion in 2017. Mr. Soni was also the CFO at Pharmacyclics, Inc., which, along with the leadership of Robert W. Duggan and Dr. Maky Zanganeh, was sold to AbbVie Inc. for $21 billion in 2015. In addition to his continuing board service to Summit, he serves on the Board of Directors of Pulse Biosciences, Inc. In conjunction with joining Summit as COO, Mr. Soni invested $5.0 million in the Company via a private placement.
Based on the accomplishments of the Company, including our deal to in-license ivonescimab and the operational progress that has been achieved since, the following elevated appointments have been made from current leaders at Team Summit:
Dave Gancarz as Chief Business & Strategy Officer
Urte Gayko, PhD, as Chief Regulatory, Quality, & Pharmacovigilance Officer
Fong Clow, DSc, as Chief Biometrics Officer
Allen S. Yang, MD, PhD, as Chief Medical Officer
H. Jack West, MD, joined Summit as Vice President of Clinical Development. Dr. West brings over 25 years of experience as a practicing thoracic oncologist; he joined Summit from City of Hope, one of the nation’s leading cancer treatment and research centers. At City of Hope, he was the Vice President of Network Strategy at AccessHope, as well as an Associate Professor and practicing medical oncologist. Prior to joining City of Hope, Dr. West spent over 15 years at Providence Health & Services, including time as the Medical Director of the Thoracic Oncology Program. As a practicing physician, Dr. West earned his medical degree from Harvard Medical School, was the Howard Hughes Medical Student Research Fellow at Massachusetts General Hospital, and did his medical oncology fellowship training at the University of Washington Fred Hutchinson Cancer Research Center.
Laura Chow, MD, joined Summit as Senior Vice President of Clinical Development. Dr. Chow brings nearly two decades of experience as a practicing medical oncologist and clinical researcher. She was previously a professor and Director of the Head & Neck and Lung Cancer Program at Dell Medical School and University of Texas at Austin. Prior to joining the University of Texas, Dr. Chow was a professor at the University of Washington Fred Hutchinson Cancer Research Center where she was a clinical researcher in lung cancer, thyroid cancers, head and neck cancers, and novel immunotherapies and anti-angiogenic agents. Dr. Chow has participated in advisory boards for multiple novel immunotherapies, including the early PD-1 therapies that now represent some of the most significant cancer therapies in present time. Dr. Chow earned her medical degree from the University of British Columbia and performed her residency at the University of Alberta.
Financial Highlights

Aggregate cash and cash equivalents, restricted cash, short-term investments, and receivables on September 30, 2023 totaled $200.5 million as compared to $654.7 million on December 31, 2022.
Our cash, cash equivalents, restricted cash, and short-term investments on September 30, 2023 was $198.9 million as compared to $648.6 million on December 31, 2022. Accounts receivable and research and development tax credits receivable on September 30, 2023 were $1.6 million as compared to $6.1 million on December 31, 2022.
Our short-term investments consist of U.S. treasury securities.
Our current notes payable balance at September 30, 2023 was $100.0 million, which is due in September 2024.
Based on our current cash and investments position, current operating plans, and with the $100.0 million notes payable due in September 2024, we have sufficient funds to operate into the second half of 2024.
Net loss for the three and nine months ended September 30, 2023 was $21.3 million and $578.4 million, respectively. Net loss for the three and nine months ended September 30, 2022 was $21.4 million and $59.6 million, respectively.
The net loss for the nine months ended September 30, 2023 includes one-time in-process research and development expenses associated with the in-licensing of ivonescimab from Akeso of $520.9 million.
Operating cash outflow for the nine months ended September 30, 2023 and 2022 was $57.3 million and $46.8 million, respectively.
Third Quarter 2023 Earnings Call

Summit will host an earnings call this morning, Tuesday, November 7, 2023, at 9:00am ET. The conference call will be accessible by dialing (888) 210-3702 (toll-free domestic) or (646) 960-0191 (international) using conference code 5785899. A live webcast and instructions for joining the call are accessible through Summit’s website www.smmttx.com. An archived edition of the webcast will be available on our website after the call.

On November 7, 2023 BPGbio, Inc., a leading biology-first AI-powered biopharma that focuses on oncology, neurology, and rare diseases, reported plans to present on their groundbreaking AI-developed therapeutics portfolio at the upcoming INV€$TIVAL Showcase in partnership with Jefferies, being held on November 13, 2023 in London, United Kingdom (Press release, BPGbio, NOV 7, 2023, View Source [SID1234637203]).

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"We’re thrilled to present the progress of our AI-developed late-stage clinical assets to investors, industry peers and partners as we continue to advance our pipeline"

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BPGbio will present as part of the event’s Biotech Late Growth Stage track. BPGbio’s President and CEO, Niven R. Narain, PhD, and Executive Chairman Daniel Elliott will detail the company’s progress in advancing BPM31510, their lead drug candidate currently in Phase 2b and Phase 2a trials for Glioblastoma Multiforme (GBM) and Pancreatic Cancer, respectively. Last month, an independent medical advisory board recommended advancement into phase 2b trials for pancreatic cancer. BPM31510 for pancreatic cancer has received orphan drug designation from the U.S. Food and Drug Administration. BPM31510 acts by targeting the mitochondrial machinery and tumor microenvironment (TME) to create a metabolic shift in cancer cells, leading to cancer cell death.

"We’re thrilled to present the progress of our AI-developed late-stage clinical assets to investors, industry peers and partners as we continue to advance our pipeline," said Dr. Narain. "The success of our lead candidate, BPM31510, in clinical trials underscores our biology-first approach to AI drug discovery, which guided our development team throughout the process and optimized our clinical trials with the appropriate patient cohort. We eagerly anticipate advancing these trials, building on our early successes, and applying this approach to other aggressive cancers and diseases with significant unmet medical needs."

The executives will also provide insights into the company’s growing portfolio of therapeutic targets and candidates, including several that are in late-stage clinical trials, which have been identified through BPGbio’s proprietary AI-powered NAi Interrogative Biology Platform. This platform identifies targets, biomarkers, and drugs and assists the development team through both the developmental and clinical trial stages. NAi is now commercially available to pharma, academic and government organizations. The NAi Platform consists of an industry leading 100,000 sample, clinically annotated biobank, with purpose-built Bayesian AI. The platform uses the world’s current fastest supercomputer, Frontier, at Oak Ridge National Laboratory (ORNL), making it the only fully integrated high-performance computing (HPC) platform in the biopharmaceutical industry for AI-driven target nomination, discovery, and molecule design.

BPGbio’s therapeutic pipeline also includes drug candidates for epidermolysis bullosa (EB, orphan drug), squamous cell carcinoma (SCC, orphan drug), sarcopenia, solid and liquid tumors, Huntington’s disease (orphan drug) and Parkinson’s disease.

The company’s diagnostic pipeline includes its prostate diagnostic test pstateDx, as well as tests being developed and validated for the detection of Parkinson’s disease (ParkinsonDx), pancreatic cancer (PancDx), breast cancer, and liver disease.

For more information on the conference, visit: View Source

On November 7, 2023 Nutcracker Therapeutics, Inc., a biotechnology company dedicated to developing transformative RNA therapies through its proprietary technology platform, reported preclinical data for two of its therapeutic candidates: its latest therapeutic candidate, NTX-471, which targets CD47; and the company’s lead mRNA candidate targeting human papillomavirus (HPV)-driven tumors, NTX-250 (Press release, Nutcracker Therapeutics, NOV 7, 2023, View Source [SID1234637202]). These data were presented at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper)’s (SITC’s) 38th Annual Meeting.

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CD47 molecules are transmembrane glycoproteins that signal macrophages not to eat the cells on which they are expressed by binding to signal regulatory protein alpha (SIRPa). Anemia is the most common adverse effect of CD47-targeting molecules, since red blood cells also express CD47. NTX-471 is being developed to specifically target CD47 on cancerous cells with unique mRNA-encoded compositions.

Nutcracker’s scientists engineered bivalent, tetravalent, hexavalent, and octavalent RNA-encoded SIRPa proteins and bispecific SIRPa-antiCCR4 molecules. The performance of these molecules were then assessed in vivo and in vitro. Key highlights of the data include:

The octavalent variant’s cytotoxic activity was similar to that of anti-CD47 molecules currently in clinical trials. But, most importantly, the Nutcracker molecules showed little-to-no binding to red blood cells in vitro
Administering mice with formulated mRNA molecules encoding the tetravalent, octavalent, and bispecific SIRPa fully eradicated established subcutaneous tumors, and resulted in robust protein expression (~10-100ug/ml) with high purity/homogeneity similar to, or better than, DNA-expressed proteins
"We’re excited to share our first set of data on NTX-471 with the scientific community," said Executive Vice President of Research and Early Development Samuel Deutsch, Ph.D. "It’s no secret that anti-CD47 therapeutics have recently hit many roadblocks, and have often struggled to address anemic side effects in patients. Using our proprietary platform and the Nutcracker Manufacturing Unit, our team was able to design and quickly produce multiple RNA molecules to assess in vivo. Through our continued work, we are hopeful that NTX-471 will prove to be a viable solution in using CD47 to eradicate tumor cells, while leaving red blood cells untouched."

Further, Nutcracker presented data on a murine version of its lead candidate, NTX-250, labelled mNTX-250. The lead indication for NTX-250 is cervical intraepithelial neoplasia CIN, a precancerous condition caused by HPV infection, which can progress to cervical cancer if left untreated. HPV-16 is the most prevalent high-risk HPV strain.

Nutcracker compared the activity of mNTX-250 to NTX-010. NTX-010 contains IL-12 and LIGHT components found in NTX-250, but lacks HPV antigens (the components of NTX-250 are detailed in previous communications). Key highlights of the data include:

Two doses of mNTX-250 treatment eradicated well-established HPV16-transformed tumors, and improved overall survival in mice. The treated animals also generated significant numbers of HPV-16 E7 antigen-specific T cells
All treated mice with eradicated tumors showed complete rejection when rechallenged
Mice treated with NTX-010 generated fewer HPV16 antigen-specific T cells. When rechallenged, 6 out of 11 NTX-010-treated mice showed tumor growth
"We developed our platform, including the Nutcracker Manufacturing Unit, specifically to fast track early R&D work for RNA therapies, and to efficiently produce them once ready for patients," said Chief Executive Officer Igor Khandros, Ph.D. "The data we presented at SITC (Free SITC Whitepaper) are a testament to the power of RNA, but also what a solution designed specifically for this modality can enable for drug developers. For example, with NTX-471, delivering mRNA, which encodes anti-CD47 proteins, offers a more straightforward method versus producing the complex proteins using a traditional cell line paradigm. Moreover, modifying the RNA sequence of the prospective anti-CD47 molecule is far more efficient than engineering the final protein product. Our platform has made it possible for Nutcracker to lay a strong and early foundation for our future therapeutic work."

On November 7, 2023 ENB Therapeutics, Inc., a clinical-stage biopharmaceutical company focused on oncology and immunology, reported top-line results from the dual combination arm of the Phase 1b ENBOLDEN-101 study, evaluating ENB-003 in combination with Merck’s anti-PD-1 therapy KEYTRUDA (pembrolizumab) in patients with advanced refractory cancers (Press release, ENB Therapeutics, NOV 7, 2023, View Source [SID1234637201]). The results show encouraging objective responses, disease control and extended progression-free survival in patients with platinum resistant/ refractory ovarian cancer (PROC). The poster, entitled, "ENB-003, an ETBR antagonist, in combination with pembrolizumab, shows promise in microsatellite stable platinum refractory/resistant ovarian cancer: Data from the ENBOLDEN-101 Phase 1B study" was presented on November 3, 2023 at a poster session at the SITC (Free SITC Whitepaper) 2023 meeting, was held November 1-5, in San Diego, California, USA.

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The data included 5 patients with metastatic microsatellite stable (MSS) PROC who had disease progression after one or more previous lines of treatment. Study treatment consisted of an initial 7-day run-in period of ENB-003 monotherapy, followed by repeated 3-week cycles of ENB-003 in combination with KEYTRUDA.

The data demonstrated that the treatment regimen was safe and well tolerated. The objective response rate (ORR) and disease control rate (DCR- patients exhibiting a response or stable disease) in MSS PROC was 40% and 80% respectively (N=5), including 2 patients with partial responses showing a 95% and 33% reduction in tumor burden respectively, as well as 4 patients with stable disease; 80% of PROC patients demonstrated shrinkage of target lesions overall. The 8-month progression-free survival rate was 60%. This compares favorably with a historical ~20% progression-free survival data at 6 months for single agent anti-PD1 and an ~8% ORR and an ~22% DCR.

"These data, demonstrate that ENB-003 in combination with KEYTRUDA is safe, with encouraging signs of clinical activity and support the combination’s potential to become an effective immunotherapy regimen for MSS primary PROC – a disease that has responded very poorly to available treatments," stated Sumayah Jamal, MD-Ph.D., President, Chief Scientific Officer, and Co-Founder of ENB Therapeutics. "We are extremely pleased with the top-line results from this ongoing study. We look forward to continuing our collaboration with Merck and anticipate initiating Part 2 of the study next year." For more information on this Phase 1/2a study, see NCT04205227.

KEYTRUDA is a registered trademark of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA.

About ENB-003

ENB-003 is a selective endothelin B receptor (ETBR) inhibitor that, in preclinical studies, enhances efficacy of CAR-T and anti-PD-1 in solid tumors across multiple cancer types in preclinical studies. In an ongoing multi-center Phase 1/2 clinical trial, early efficacy signals suggest that ENB-003 overcomes resistance to pembrolizumab in heavily pre-treated drug resistant cancer patients. The Phase 2 portion of the ENB-003 + pembrolizumab combination study is expected to start in the first half of 2024. The trial will enroll MSS primary PROC, as well as MSS pancreatic cancer patients and patients with other advanced solid tumors that have failed standard of care.

On November 7, 2023 BostonGene, a leading provider of AI-driven, molecular and immune profiling solutions, and LegoChem Biosciences, Inc. (LCB), a clinical-stage biopharmaceutical company developing next-generation, antibody-drug conjugates (ADCs), reported a collaboration to support the Phase I/II study of LCB84, a TROP2-directed ADC, in patients with advanced cancers (Press release, BostonGene, NOV 7, 2023, View Source [SID1234637200]). This first-in-human study is being conducted at leading cancer institutions in the US and Canada to evaluate the safety and preliminary efficacy of LCB84, both as a single-agent therapy and in combination with an immune checkpoint inhibitor (anti-PD-1 antibody).

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"BostonGene’s integrated analytic and AI capabilities will provide us with crucial insights towards developing breakthrough cancer treatments."

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"We partnered with BostonGene in order to validate theorized mechanisms of ADC efficacy and uncover novel biomarkers to improve patient selection as LegoChem Biosciences progresses towards further clinical validation of our ADC platform technology, enabling safer and more efficacious therapies for cancer patients," said Director of Drug Development Stephen Slocum, PhD at LegoChem Biosciences. "BostonGene’s integrated analytic and AI capabilities will provide us with crucial insights towards developing breakthrough cancer treatments."

"We are excited to collaborate with LCB to support the development of their novel, TROP2-directed ADC, LCB84, and to address the high unmet need in cancer for improved tumor targeting, safety and efficacy," said Andrew Feinberg, President and CEO at BostonGene.

Added Chief Medical Officer Nathan Fowler, MD, "BostonGene’s proprietary discovery platform merges a deep understanding of the human immune system and cancer biology with unparalleled software expertise and capacity. With a pragmatic, results-oriented team approach, we are driven by the potential for a direct impact on the lives of cancer patients. Our accelerated biomarker discovery algorithms support optimized "matching" of patients with therapies that can effectively target the unique characteristics of their cancer."

BostonGene will serve as the study’s central laboratory and analytic partner for exploratory biomarkers, performing in-depth, multi-omic profiling of patients’ tumor tissue and blood samples, including whole-exome sequencing (WES), whole-transcriptome sequencing (RNAseq) of tumor tissue from matched tumor biopsies on the study, and immunoprofiling to identify hundreds of different cell types from a single blood sample. Leveraging its advanced AI and machine learning platforms, BostonGene will also deliver comprehensive analytics to identify predictive biomarkers and optimize the selection of patients most likely to benefit from treatment.

Each patient’s tumor has a unique molecular "fingerprint" that can be identified with BostonGene’s differentiated analytic and software platforms for comprehensive, real-time, cost-efficient results to support the delivery of highly personalized cancer therapies that give patients the best chance of durable responses.