On June 26, 2023 Larkspur Biosciences reported it revealed that one of their lead programs is a first-in-class B cell checkpoint, TIM-1 (Press release, Larkspur Biosciences, JUN 26, 2023, View Source [SID1234633156]). This announcement follows the publication by Larkspur co-founder Vijay K. Kuchroo, DVM, PhD (Samuel L. Wasserstrom Professor, Neurology, Harvard Medical School; Senior Scientist, Neurology, Brigham and Women’s Hospital) in the journal Nature of TIM-1 as a targetable checkpoint protein central to B-cell anti-tumor activity.

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Immunotherapies targeting T cells have transformed the treatment of many types of cancers. Recent discoveries have highlighted that the presence of tertiary lymphoid structures in tumors – areas of B cell and T cell activation – are associated with positive responses to checkpoint blockade. Larkspur’s approach addresses the unique ways that tumors hijack the immune system, targeting bottlenecks that tumors use to subvert the immune system in order to develop precision immunotherapies for molecularly defined patient populations. This newly disclosed program adds a unique way to use B cells to drive anti-tumor responses.

"The discovery of this novel B cell checkpoint protein, outlined in the Nature publication, unlocks the potential of targeting B cells to enhance immunotherapy responses," said Dr. Kuchroo. "These findings support broadening the application of immune checkpoint blockade in cancer immunotherapy and provide a clear path to translation, which Larkspur is advancing within its pipeline."

Dr. Kuchroo, along with lead author Lloyd Bod, PhD (Mass General Cancer Center), and colleagues, discovered a type of B cell expressing TIM-1 expanded as tumors grew in melanoma. Using an antibody to TIM-1, they discovered that targeting TIM-1 and PD-1 in the melanoma model led to a better anti-tumor response, underscoring the potential of targeting both B cells and T cells in cancer.

"It has recently been shown that the presence of B cells at the tumor is associated with positive responses to checkpoint blockade for cancer patients," said Catherine Sabatos-Peyton, PhD, CEO of Larkspur Biosciences. "TIM-1 offers a novel way to harness the power of B cells at the tumor and potentially drive more meaningful anti-tumor responses for more patients. We look forward to continuing to progress our TIM-1 program as part of our mission to create the next precision immunotherapies to outsmart cancer."

The Nature article titled "B-cell-specific checkpoint molecules that regulate anti-tumour immunity" was published on June 21, 2023. The research briefing "Uncovering a role for B cells in antitumour immunity" provides a summary of the article.

On June 26, 2023 Sermonix Pharmaceuticals Inc., a privately held biopharmaceutical company developing innovative therapeutics to treat metastatic breast and gynecological cancers harboring ESR1 mutations, reported that an article analyzing its use of both traditional enrollment methods and a just-in-time model for its Phase 2 ELAINE-2 clinical trial was published in JCO Clinical Cancer Informatics (JCO CCI) (Press release, Sermonix Pharmaceuticals, JUN 26, 2023, View Source [SID1234632934]).

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The article, "Operational Metrics for the ELAINE-2 Study Combining a Traditional Approach with a Just-in-TIME Model," details Sermonix’s use of two distinct enrollment methods for its second Evaluation of Lasofoxifene in ESR1 Mutations (ELAINE) study, which recruited patients from 2020-2021. One method was a traditional approach that included site selection, institutional review board (IRB) and contract approval, and trial activation prior to a patient being identified for enrollment. The second method used the Tempus TIME Trial Network that would rapidly open the trial, at the site of care, after identifying a patient with a mutation of interest and eligibility for the trial. Sermonix was able to leverage Tempus’ network of individual clinical sites that use a pre-approved clinical trial agreement and regulatory process, as well as a central IRB.

"Sermonix’s collaboration with Tempus for ELAINE-2 trial proved to be a great success story, allowing us to more rapidly and efficiently recruit eligible patients from a wider area, rather than relying only on traditional sites," said Paul Plourde, M.D., vice president of oncology clinical development at Sermonix. "Based on these results, we are again thrilled to work with Tempus in our registrational Phase 3 ELAINE-3 study."

ELAINE-2 enrolled 29 patients over 8.5 months, besting its anticipated enrollment period of 12-18 months. Six traditional and 10 TIME Trial sites participated. The duration for full clinical trial agreement execution averaged 200.5 days for traditional sites, compared to 7.6 days for TIME Trial sites. Average IRB approval time was 27.5 days and three days respectively. Average time from study activation to first consent was 33.3 days and 8.8 days respectively. The first seven patients enrolled were at TIME Trial sites and the first patient was on-study 115 days before a traditional site equivalent. Traditional sites consented 23 patients and enrolled 16, while TIME trial sites consented 16 and enrolled 13.

"So many prospective patients want to participate in clinical trials but do not live close enough to the major academic medical centers that traditionally serve as investigational sites," said Plourde. "The just-in-time model provides an important opportunity to a greater diversity of patients. These results demonstrate the value of employing both models for biomarker-driven studies."

Tempus is an industry leader analyzing multimodal data to identify actionable clinical trial options for cancer patients. Through its TIME Trial Network, 1,500 oncologists and their patients have access to a large portfolio of cutting-edge precision medicine trials.

"The ELAINE-2 study is a great example of how Tempus’ platform can identify patients for these biomarker-driven studies and then rapidly activates sites closer to home in a fraction of time it has historically taken," said Matthew Cooney, M.D., vice president of therapeutic development, oncology, at Tempus. "This approach creates greater access to cutting-edge, investigational therapies to patients around the country while also accelerating study times."

ELAINE-3 is a registrational Phase 3 clinical study comparing targeted lasofoxifene, Sermonix’s lead investigational drug, in combination with Eli Lilly and Company’s CDK 4/6 inhibitor abemaciclib versus fulvestrant plus abemaciclib in pre- and post-menopausal subjects with locally advanced or metastatic ER+/HER2- breast cancer with an ESR1 mutation.

JCO CCI is an online-only, interdisciplinary journal publishing clinically relevant research based on biomedical informatics methods and processes applied to cancer-related data, information, and images.

Sermonix’s article is an open-access submission. To read the published article, visit JCO CCI’s website. To learn more about the ELAINE studies, visit ElaineStudy.com.

About Lasofoxifene

Lasofoxifene is an investigational novel endocrine therapy in clinical development which has demonstrated robust target engagement as an ESR1 antagonist in the breast, particularly in the presence of ESR1 mutations. Lasofoxifene has demonstrated anti-tumor activity as monotherapy and in combination with abemaciclib in Phase 2 studies and has unique tissue selectivity distinguishing it from other current and investigational endocrine therapies, with beneficial effects seen on vagina and bone in previous clinical studies. Lasofoxifene, which Sermonix licensed globally from Ligand Pharmaceuticals Inc. (NASDAQ:LGND), has been studied in previous comprehensive Phase 1-3 non-oncology clinical trials in more than 15,000 postmenopausal women worldwide. Lasofoxifene’s bioavailability and activity in mutations of the estrogen receptor could potentially hold promise for patients who have acquired endocrine resistance due to ESR1 mutations, a common finding in the metastatic setting and an area of high unmet medical need. Lasofoxifene’s novel activity in ESR1 mutations was discovered at Duke University and Sermonix has exclusive rights to develop and commercialize the product in this area. Lasofoxifene, a novel targeted and tissue selective oral endocrine therapy could, if approved, play a critical role in the precision medicine treatment of advanced ER+ breast cancer.

On June 26, 2023, Kiromic BioPharma, Inc. (the "Company") reported to have issued a 25% Senior Secured Convertible Promissory Note (the "Note") to an accredited investor (Filing, Kiromic, JUN 26, 2023, View Source [SID1234632931]). The Note has a principal amount of $2,400,000, bears interest at a rate of 25% per annum (the "Stated Rate") and matures on June 26, 2024 (the "Maturity Date"), on which the principal balance and accrued but unpaid interest under the Note shall be due and payable. The Stated Rate will increase to 27% per annum or the highest rate then allowed under applicable law (whichever is lower) upon occurrence of an event of default, including the failure by the Company to make payment of principal or interest due under the Note on the Maturity Date, and any commencement by the Company of a case under any applicable bankruptcy or insolvency laws.

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The Note is convertible into shares (the "Conversion Shares") of the Company’s common stock, par value $0.001 per share (the "Common Stock"), at an initial conversion price of $6.50 per share (the "Conversion Price"), subject to a beneficial ownership limitation equivalent to 9.99% (the "Beneficial Ownership Limitation").

The unpaid principal of and interest on the Note constitute unsubordinated obligations of the Company and are senior and preferred in right of payment to all subordinated indebtedness and equity securities of the Company outstanding as of the Issuance Date; provided, however, that the Company may incur or guarantee additional indebtedness after the Issuance Date, whether such indebtedness are senior, pari passu or junior to the obligations under the Note, which are secured by all of the Company’s right, title and interest, in and to, (i) all fixtures (as defined in the Uniform Commercial Code, the "UCC") and equipment (as defined in the UCC), and (ii) all of the Company’s intellectual property as specified in the Note, subject to certain exclusions as described in the Note.

The foregoing description of the Note is qualified in its entirety by reference to the full text of such Note, a copy of which is attached hereto as exhibit 10.1 and incorporated herein by reference.

On June 26, 2023 Ariceum Therapeutics (Ariceum), a private biotech company developing radiopharmaceutical products for the diagnosis and treatment of certain hard-to-treat cancers, and Eurofins CDMO (part of Eurofins’ network of companies – Eurofins Scientific SE (EURONEXT PARIS: ERF)), a leading global Contract Development and Manufacturing Organization, reported a strategic partnership which will see Eurofins CDMO provide Clinical Trial Supply services to support Ariceum’s current Phase I/II clinical studies in Australia, as well as future clinical studies (Press release, Ariceum Therapeutics, JUN 26, 2023, View Source [SID1234632926]).

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Initial work on this strategic partnership began one year ago, and the past 12 months have seen the establishment of infrastructure required to support and supply Ariceum’s clinical trials. Services provided to Ariceum Therapeutics by Eurofins CDMO are facilitated in the Eurofins CDMO EUR site in Lentilly, France, which specializes in Clinical Trial Supply services, and comprise, among other services, Qualified Person (QP) release of Drug Substance into Europe, Storage of Drug Substance, Packaging Drug Product, Cold Chain Management (-20oC and 2/8oC) and the management of deliveries of Drug Product to investigational sites. Eurofins CDMO’s short internal process lead times provide Ariceum with the required flexibility to respond to project needs.

Manfred Rüdiger, PhD, Chief Executive Officer of Ariceum Therapeutics, said: "Ariceum is pleased to partner with renowned Eurofins CDMO for the supply of its studies. Over the past year Eurofins CDMO has proven to be a flexible and reliable partner. Through this partnership, Ariceum has established the infrastructure required to support and supply the recently initiated Phase I/II trials in Australia as well as future clinical trials."

On June 26, 2023 ALX Oncology Holdings Inc., ("ALX Oncology") (Nasdaq: ALXO), a clinical-stage immuno-oncology company developing therapies that block the CD47 checkpoint pathway, reported that evorpacept, a next-generation CD47 blocker, has received orphan drug designation ("ODD") from the European Commission ("EC") for the treatment of patients with gastric cancer (Press release, ALX Oncology, JUN 26, 2023, View Source [SID1234632889]). This ODD indication includes both gastric cancer and gastroesophageal junction adenocarcinoma (collectively "GC"). The U.S. Food and Drug Administration ("FDA") also granted ODD to evorpacept for the treatment of patients with GC as previously announced in January 2022.

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"Receiving orphan drug designation from both the EC and the FDA represents a significant regulatory achievement for ALX Oncology and signifies the growing recognition of evorpacept as a potential new drug to improve clinical outcomes in patients with GC," said Sophia Randolph, M.D., Ph.D., Chief Medical Officer, ALX Oncology. "Evorpacept has demonstrated promising and consistent anti-cancer activity in the solid tumor setting, and we look forward to presenting data in the second half of 2023 for ASPEN-06, a randomized Phase 2 trial of evorpacept in combination with trastuzumab, paclitaxel and CYRAMZA (ramucirumab) for the treatment of patients with HER2-positive GC."

Orphan drug designation is granted by the EC for medicines in development to treat rare conditions affecting no more than five in 10,000 people in the European Union, provided there is no other satisfactory treatment option or the medicine can be of significant benefit to those affected by the condition. Medicines that are granted orphan drug designation by the EC qualify for financial and regulatory incentives including protocol assistance, possible exemptions or reductions in certain regulatory fees, and, if approved for marketing, ten years of market exclusivity in the European Union.

About Gastric Cancer and Gastroesophageal Junction Cancer (section to be updated)

Gastric cancer begins in the cells lining the inner wall of the stomach and spreads through the outer layers and eventually the body as it grows. Approximately 17 percent of all GC patients have HER2-positive disease, and the five-year survival rate is only 5.5 percent for those patients diagnosed with metastatic disease (SEER). The National Cancer Institute estimates there will be over 26,000 newly diagnosed cases of GC and 11,000 deaths in the U.S. in 2023. In comparison, GC is significantly more common in Europe with over 130,000 newly diagnosed cases and 96,000 deaths in 2020 (Globocan).