On December 12, 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, DEC 12, 2023, View Source [SID1234641113]). The Note has a principal amount of $2,000,000, bears interest at a rate of 25% per annum (the "Stated Rate") and matures on December 12, 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.

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!

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 $2.50 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 December 12, 2023 Molecure S.A. ("Molecure": WSE: MOC) a clinical stage biotechnology company developing first-in-class small molecule drug candidates that directly modulate unexplored protein and mRNA targets to treat multiple incurable diseases, reported in vitro that small molecule binding to the selected mRNA fragment inhibit the translation of the protein encoded by that mRNA (Press release, Molecure, DEC 12, 2023, View Source [SID1234640058]). Confirmation of the mechanism of stopping the pathological proteins translation in a dose dependent manner, represents a significant milestone in the development of the mRNA platform and has been one of the strategic goals of the Company during 2023-2025.

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!

‘The initial stage of scientific research in the mRNA platform involved identifying the structure of the mRNA region with high potential for binding small molecules (druggable regions). After confirming the functionality of this region, we conducted modeling of its tertiary structure, a necessary step to proceed to virtual screening. The binding of the best compounds to the mRNA fragment was confirmed using biophysical methods. The identified molecules, directly interacting with the mRNA fragment, demonstrated inhibition of the protein translation encoded by the given mRNA in a dose dependent manner. These results mark our anticipated Proof-of-Concept (PoC) for the first mRNA target in the platform. This big success achieved by our scientists validated of our ambitious approach for platform development. The next stage will involve evaluating the possibilities of continued preclinical and potentially clinical development of lead molecules optimized in this program. The company is also expanding its in-house expertise in identifying new mRNA regions that may serve as attractive therapeutic targets’ says Dr. Zbigniew Zasłona, Chief Scientific Officer, and Member of the Board at Molecure S.A.

‘We are proud to have achieved the in vitro Proof-of-Concept (PoC) for the first hit molecules developed in the mRNA platform. As the result of combining creativity, innovative approach, and the determination of our team in discovery of new molecules, leveraging strong in-house expertise in drug design using advanced digital methods. It confirms that we are among the global leaders in the field of mRNA-targeting small molecule drugs, a breakthrough technology with the potential to change the paradigm of treating many diseases, where the protein structure itself prevents direct interaction with small molecules (so-called undruggable targets). The development of the mRNA discovery platform, alongside our two clinical programs, is one of Molecure’s strategic priorities. Achieving the in vitro proof-of-concept this year, as outlined in our 2023-2025 strategy, is a significant milestone that we have reached and confirmed as planned. This will enable us to intensify partnering discussions and increase the likelihood of establishing commercially attractive collaborations with industry partners’ says Dr. Marcin Szumowski, CEO, and President of the Board at Molecure S.A.

The business model of the Company in the mRNA platform involves a hybrid approach. Molecure aims to develop its own proprietary projects targeting internally selected mRNA structures as well as provide services to external companies in the biopharmaceutical sector. These services involve validating mRNA fragments chosen by the client as therapeutic targets. This approach enables partnering and the generation of revenue as early as the optimization stage of active binders, i.e., after achieving in vitro Proof-of-Concept (PoC) for the relevant mRNA target.

Molecure is one of the few biotechnology companies globally developing small molecule drugs that directly interact with mRNA targets.

On December 12, 2023 Sermonix Pharmaceuticals Inc., a privately held biopharmaceutical company developing innovative therapeutics to specifically treat metastatic breast cancers (mBC) harboring ESR1 mutations, reported the three poster presentations examining clinical data tied to Sermonix’s Evaluation of Lasofoxifene in ESR1 Mutations (ELAINE) studies (Press release, Sermonix Pharmaceuticals, DEC 12, 2023, View Source [SID1234638576]). The presentations were initially shared last week at the 2023 San Antonio Breast Cancer Symposium (SABCS).

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!

"Secondary analysis of our ELAINE study results reveals reassuring pharmacokinetic data, further confidence in lasofoxifene’s ability to be effectively combined with abemaciclib, and a better understanding of the baseline genomic alterations found in patients with ESR1 mutations," said Dr. Paul Plourde, Sermonix vice president for clinical oncology development. "We are delighted to be actively screening and enrolling patients into our Phase 3 ELAINE-3 registrational trial at institutions across the U.S., and with the EU to closely follow."

One poster addressed pharmacokinetics (PK) of lasofoxifene as a monotherapy and in combination with Eli Lilly and Company’s CDK4/6 inhibitor abemaciclib (Verzenio). Key takeaways included:

PK data for lasofoxifene 5 mg/day were consistent with previous clinical trials, resulting in similar steady-state concentrations in patients across several studies.
Addition of abemaciclib to lasofoxifene did not appear to alter the PK of lasofoxifene in ELAINE-2 compared with monotherapy in ELAINE-1, suggesting little to no drug-drug interaction.
Abemaciclib concentrations in ELAINE-2 were consistent with previous monotherapy data, suggesting no impact of lasofoxifene on abemaciclib PK.
A second poster discussed baseline genomic alterations and the activity of lasofoxifene and abemaciclib during the ELAINE-2 study. Key results/conclusions included:

In 26 of the 29 patients (median age 60 years) enrolled, ESR1 mutations were identified at baseline by the Guardant360 CDx test. The profiling demonstrated that other genomic alterations are frequently detected concurrently with ESR1 mutations in the endocrine-resistant setting, in line with previous findings among patients with hormone receptor-positive mBC.
Co-alterations in ESR1 and other genes associated with treatment resistance did not appear to compromise the efficacy of lasofoxifene plus abemaciclib in ELAINE-2.
A third poster offered a trial-in-progress update on ELAINE-3, a 400-patient Phase 3 study assessing the efficacy and safety of lasofoxifene in combination with abemaciclib in treating locally advanced or ER+/HER2- mBC with an ESR1 mutation. ELAINE-3 enrollment is now underway.

To learn more about Sermonix Pharmaceuticals and lasofoxifene, visit View Source For more information about the ELAINE studies, visit View Source

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 a CDK4/6 inhibitor 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 December 12, 2023 Obsidian Therapeutics, Inc., a clinical-stage biotechnology company pioneering engineered cell and gene therapies, reported positive top-line results from the ongoing first-in-human, Phase 1 clinical trial evaluating the safety and efficacy of OBX-115, Obsidian’s lead engineered tumor-infiltrating lymphocyte (TIL) cell therapy candidate, in patients with metastatic melanoma that has relapsed and/or is refractory to prior immune checkpoint inhibitor (ICI) therapy (NCT05470283) (Press release, Obsidian Therapeutics, DEC 12, 2023, View Source [SID1234638520]).

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!

OBX-115 is an investigational novel IL2-sparing engineered TIL cell therapy armed with pharmacologically regulatable membrane-bound IL15 designed to enhance persistence, anti-tumor activity, and clinical safety of TIL cell therapy relative to unengineered TIL therapy plus high-dose IL2.

The first six patients treated with OBX-115 were enrolled by Rodabe Amaria, M.D., professor of Melanoma Medical Oncology and principal investigator of the study at The University of Texas MD Anderson Cancer Center. Patients were heavily pre-treated, and all had progressed on anti–PD-1 and anti–CTLA-4 therapy with disease that was primary-resistant to ICI therapy. At a median follow-up of 18 weeks (December 1st, 2023 data cut-off), a 50% investigator-assessed objective response rate (ORR) using RECIST 1.1 criteria was observed. Two complete responses and one partial response were achieved, with a disease control rate (DCR) of 100%.

To date, no dose-limiting toxicities have been observed, and the treatment-emergent adverse event profile was consistent with that of lymphodepletion. OBX-115 was manufactured from core-biopsies of tumors for the majority of patients by CTMC, a joint venture between MD Anderson and National Resilience, Inc. Additionally, early data from the study support validation of Obsidian’s cytoDRiVE technology for the pharmacologic regulation of membrane-bound IL15 to enable controlled proliferation, enhanced persistence and anti-tumor activity of adoptive T-cell therapies.

"The OBX-115 data show its potential to be a meaningful advancement in the treatment of metastatic melanoma and TIL cell therapy," said Parameswaran Hari, M.D., M.S., Chief Development Officer of Obsidian Therapeutics. "These initial topline results support the promise for OBX-115 to drive responses in this heavily pre-treated patient population and facilitate the expansion of TIL cell therapy in melanoma to a broad group of patients without the need for IL2."

In addition, Obsidian announced today that it has enrolled the first patient in its multicenter Phase 1/2 study of advanced or metastatic melanoma resistant to ICI therapy. This study allows multiple centers to have access to OBX-115 and is currently enrolling patients. Additional details may be found at clinicaltrials.gov, using identifier: NCT06060613.

"These positive results underscore the potential for OBX-115 TIL cell therapy to offer patients with metastatic melanoma a differentiated TIL therapy without the need for IL2," said Madan Jagasia, M.D., M.S., CEO of Obsidian Therapeutics. "Furthermore, the emerging profile of OBX-115 indicates it will allow expansion of TIL cell therapy into a broad patient population, including those who may not be able to tolerate IL2 or choose not to receive it. As we look to the future, we are exploring additional indications, including non-small cell lung cancer."

About OBX-115
Obsidian’s lead investigational cytoTIL15 program, OBX-115, is a novel engineered tumor-infiltrating lymphocyte (TIL) cell therapy armed with pharmacologically regulatable membrane-bound IL15 (mbIL15). OBX-115 has the potential to become a meaningful therapeutic option for patients with advanced or metastatic melanoma and other solid tumors by leveraging the expected benefits of mbIL15 and Obsidian’s proprietary, differentiated manufacturing process to enhance persistence, anti-tumor activity, and clinical safety of TIL cell therapy. OBX-115 is being investigated in two ongoing and enrolling clinical trials in advanced or metastatic melanoma (NCT05470283 and NCT06060613).

On December 12, 2023 Toragen Inc., a San Diego-based clinical-stage biotechnology company focused on developing uniquely selective drugs targeting cancers caused by viruses, reported positive safety data from Cohort 2 of its Phase 1 trial of TGN-S11, its first drug candidate, in patients with HPV-associated cancers (Press release, Toragen, DEC 12, 2023, View Source [SID1234638519]).

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!

This Phase 1 trial is an open-label, non-randomized study in cohorts of patients with relapsed, resistant, or metastatic HPV-associated cancers. The study is being conducted in two parts: a dose escalation part and dose expansion part. The dose escalation consists of five Cohorts of three to six patients. The dose expansion will now begin in parallel with Cohort 3 of the dose escalation. Level 1 of the dose expansion part of the Phase 1 trial will be in combination with a PD-1 checkpoint inhibitor.

"Having this early safety signal for our dose escalation portion of our Phase 1 trial is yet another early milestone for Toragen," said Dr. Sandra Coufal, Toragen’s CEO. "By beginning the dose expansion portion of the Phase 1 trial in an accelerated timeframe, we bring hope of meeting an unmet medical need for HPV-cancer patients by possibly enhancing the efficacy of the PD-1 checkpoint inhibitor."