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AI Startup Lunit Secures Investment from Guardant Health in a Strategic Funding Round

On July 19, 2021 Lunit, a leading AI startup in AI-powered cancer solutions, reported a strategic investment of $26 million from Guardant Health, Inc. (Nasdaq: GH), a leading precision oncology company (Press release, Guardant Health, JUL 19, 2021, View Source [SID1234584951]).

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The deal, which includes the investment made by Guardant Health and also a groundbreaking collaboration between a liquid biopsy company and a medical AI startup, is intended to help reshape and innovate the precision oncology landscape.

Lunit has closed its Series C Tranche B funding round with the investment from Guardant Health. Lunit is expected to file for an initial public offering on the Korean Stock Exchange later this year.

At the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) 2021 annual meeting, Lunit presented that its tissue analysis platform, Lunit SCOPE, was able to find 50% more patients who would respond to immunotherapy, compared to traditional diagnostic pathology.1 Lunit has been presenting its findings at ASCO (Free ASCO Whitepaper) and American Association for Cancer Research (AACR) (Free AACR Whitepaper) since 2019.

"Artificial intelligence is rapidly gaining ground in cancer research and it’s exciting to see the excellent progress Lunit has made in developing innovative AI-powered radiology and pathology solutions that have the potential to significantly improve the diagnoses and treatment of cancer," said Helmy Eltoukhy, Guardant Health CEO. "We’re very impressed with Lunit’s approach and believe this investment will help them advance their important AI work for eventual clinical use. Through this investment, we also expect to utilize their AI platform to usher in new precision oncology products that contribute in a meaningful way to improving cancer care for patients."

"We believe that AI in the field of medicine is an inevitable future to come," said Brandon Suh, M.D., Chief Executive Officer of Lunit. "As one of the early starters and front-runners in this new and innovative field, we have been validating the effectiveness of Lunit SCOPE through various studies, and now we are pushing to show its value in clinical research and real practice. We are more than delighted to announce the investment and collaboration with Guardant Health. With our AI technology in tissue phenomics and Guardant Health’s commitment to advancing our work, we are looking forward to making impactful changes in cancer diagnosis and treatment."

OncoNano Medicine to Present at the 2nd Annual LifeSci Partners Private Company Summer Symposium

On July 19, 2021 OncoNano Medicine, Inc. reported a presentation at the 2nd Annual LifeSci Partners Private Company Summer Symposium, to be held virtually July 21-23, 2021 (Press release, OncoNano Medicine, JUL 19, 2021, View Source [SID1234584950]). Martin Driscoll, CEO of OncoNano, will present on Thursday, July 22nd at 1:30 p.m. ET.

Celsion Reports Data Safety Monitoring Board Recommendation to Continue Dosing Patients in the Phase II Portion of the OVATION 2 Study with GEN-1 in Advanced Ovarian Cancer

On July 19, 2021 Celsion Corporation (NASDAQ: CLSN), a clinical-stage company focused on DNA-based immunotherapy and next-generation vaccines, reported that following a pre-planned interim safety review of 55 as treated patients randomized in the Phase I/II OVATION 2 Study with GEN-1 in advanced (Stage III/IV) ovarian cancer, the Data Safety Monitoring Board (DSMB) has unanimously recommended that the OVATION 2 Study continue treating patients with the dose of 100 mg/m2 (Press release, Celsion, JUL 19, 2021, View Source [SID1234584949]). The DSMB also determined that safety is satisfactory with an acceptable risk/benefit, and that patients tolerate up to 17 doses of GEN-1 during a course of treatment that lasts up to six months. No dose-limiting toxicities were reported.

The OVATION 2 Study combines GEN-1, the Company’s IL-12 gene-mediated immunotherapy, with standard-of-care neoadjuvant chemotherapy (NACT) in patients newly diagnosed with Stage III/IV ovarian cancer. NACT is designed to shrink the cancer as much as possible for optimal surgical removal after three cycles of chemotherapy. Following NACT, patients undergo interval debulking surgery, followed by three additional cycles of chemotherapy to treat any residual tumor.

The OVATION 2 Study is designed with an 80% confidence interval for an observed Progression Free Survival (PFS) Hazard Ratio of 0.75, which would mean an approximate 33% improvement in risk for cancer progression when comparing the treatment arm (NACT + GEN-1) with the control arm (NACT only). GEN-1 is an immunotherapy that produces safe and durable local levels of IL-12, a pluripotent cytokine associated with the stimulation of innate and adaptive immune response against cancer. The GEN-1 nanoparticle comprises a DNA plasmid encoding IL-12 gene and a synthetic polymer facilitating plasmid delivery vector. Cell transfection is followed by persistent, local secretion of the IL-12 protein at therapeutic levels.

The Company also announced that more than 50% of the projected 110 patients have been enrolled in the OVATION 2 Study. Interim clinical data from the first 36 patients who have undergone interval debulking surgery are as follows:

Of the 36 patients who have undergone interval debulking surgery in the OVATION 2 Study:
20 patients were treated with GEN-1 at a dose of 100 mg/m² plus NACT, with 16 out of 20 patients (80%) having a complete tumor resection (R0), which indicates a microscopically margin-negative resection in which no gross or microscopic tumor remains in the tumor bed; and
16 patients were treated with NACT only, with 9 out of 16 patients (56%) having R0 resections.

When combining these results with the surgical resection rates observed in the Company’s prior Phase Ib dose-escalation trial (the OVATION 1 Study), a population of patients with inclusion criteria identical to the OVATION 2 Study, the data reflect the strong dose-dependent efficacy of adding GEN-1 to NACT:
% Patients with R0 Resections
0, 36, 47 mg/m² of GEN-1 plus NACT n=22 50 %
61, 79, 100 mg/m² of GEN-1 plus NACT n=28 82 %

The objective response rate (ORR) as measured by Response Evaluation Criteria in Solid Tumors (RECIST) criteria for the 16 patients treated with NACT only were comparable, as expected, to the 20 patients treated with GEN-1 at a dose of 100 mg/m² plus NACT, with both groups demonstrating an approximate 80% ORR.
"These findings show a consistent dose-dependent clinical response in both surgical outcome and tumor response, which is further supported by translational data of the tumor microenvironment," noted Nicholas Borys, M.D., Celsion’s executive vice president and chief medical officer. "Continuing our clinical research program at the 100 mg/m2 dose in patients with advanced-stage ovarian cancer holds promise and is strongly encouraged by our study investigators and medical advisors."

"We thank the DSMB members for their work and advice," said Michael H. Tardugno, Celsion’s chairman, president and chief executive officer. "We are encouraged by the current rate of patient recruitment and expect to complete enrollment around the end of this year. FDA Fast Track and Orphan Drug Designations for GEN-1 in advanced ovarian cancer are important for our future commercialization efforts. In addition, under the Biologics Price Competition and Innovation Act of 2009, sponsors of new, licensed biological products like GEN-1 that are approved through a Biologics License Application receive 12 years of market exclusivity. The FDA cannot license any 351(k) application for a biosimilar or interchangeable product that relies on the previously approved product as a reference for biosimilarity during this 12-year period."

In February 2021, the Company announced that GEN-1 received FDA Fast Track Designation in advanced ovarian cancer. Celsion plans to request FDA Breakthrough Therapy Designation for GEN-1 based on the encouraging clinical data announced today.

About GEN-1 Immunotherapy

GEN-1, designed using Celsion’s proprietary TheraPlas platform technology, is an IL-12 DNA plasmid vector encased in a nanoparticle delivery system, which enables cell transfection followed by persistent, local secretion of the IL-12 protein. IL-12 is one of the most active cytokines for the induction of potent anti-cancer immunity acting through the induction of T-lymphocyte and natural killer (NK) cell proliferation. The Company previously reported positive safety and encouraging Phase I results with GEN-1 given as monotherapy or a combination therapy in patients with advanced peritoneally metastasized primary or recurrent ovarian cancer, and recently completed a Phase Ib dose-escalation trial (OVATION 1 Study) of GEN-1 in combination with carboplatin and paclitaxel in patients with newly diagnosed ovarian cancer.

Provectus Biopharmaceuticals Announces Acceptance of PV-10® Neuroendocrine Cancer Abstract at European Society for Medical Oncology (ESMO) Congress 2021

On July 19, 2021 Provectus (OTCQB: PVCT) reported that data from an ongoing clinical trial of investigational cancer immunotherapy PV-10 (rose bengal disodium) for the treatment of neuroendocrine tumors (NET) metastatic to the liver (mNET) refractory to somatostatin analogs (SSAs) and peptide receptor radionuclide therapy (PRRT) (NCT02693067) will be presented at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress, to be held online from September 16-21, 2021 (Press release, Provectus Biopharmaceuticals, JUL 19, 2021, View Source [SID1234584948]).

The abstract accepted for electronic poster presentation is entitled:

"Phase I study of hepatic intralesional rose bengal disodium (PV10), an autolytic immunotherapy, in metastatic neuroendocrine neoplasms" (#4354).
About PV-10

Intralesional (IL) administration of PV-10 for the treatment of solid tumor cancers can yield immunogenic cell death within hours of tumor injection, and induce tumor-specific reactivity in circulating T cells within days.1,2,3 This IL PV-10-induced functional T cell response may be enhanced and boosted in combination with immune checkpoint blockade (CB).4 In CB-refractory advanced cutaneous melanoma, IL PV-10 may restore disease-specific T cell function, which may also be prognostic of clinical response. IL PV-10 has been administered to over 450 patients with cancers of the skin and of the liver. It is administered under visual, tactile or ultrasound guidance to superficial malignancies, and under CT or ultrasound guidance to tumors of the liver. Systemic administration of PV-10 is also undergoing preclinical study as prophylactic and therapeutic treatments for refractory and high-risk adult solid tumor cancers, and as a treatment for relapsed and refractory blood cancers.

About Rose Bengal Disodium

RBD is 4,5,6,7-tetrachloro-2′,4′,5′,7′-tetraiodofluorescein disodium, a halogenated xanthene and Provectus’ proprietary lead molecule. Provectus’ current Good Manufacturing Practices (cGMP) RBD is a proprietary pharmaceutical-grade drug substance produced by the Company’s quality-by-design (QbD) manufacturing process to exacting regulatory standards that avoids the formation of uncontrolled impurities currently present in commercial-grade rose bengal. Provectus’ RBD and cGMP RBD manufacturing process are protected by composition of matter and manufacturing patents as well as trade secrets.

An IL formulation (i.e., by direct injection) of cGMP RBD drug substance, cGMP PV-10, is being developed as an autolytic immunotherapy drug product for solid tumor cancers.

IL PV-10 is also undergoing preclinical study for relapsed and refractory pediatric solid tumor cancers, such as neuroblastoma, Ewing sarcoma, rhabdomyosarcoma, and osteosarcoma.5,6

A topical formulation of cGMP RBD drug substance, PH-10, is being developed as a clinical-stage immuno-dermatology drug product for inflammatory dermatoses, such as atopic dermatitis and psoriasis. RBD can modulate multiple interleukin and interferon pathways and key cytokine disease drivers.7

Oral formulations of cGMP RBD are undergoing preclinical study for relapsed and refractory pediatric blood cancers, such as acute lymphocytic leukemia and acute myelomonocytic leukemia.8,9

Oral formulations of cGMP RBD are also undergoing preclinical study as prophylactic and therapeutic treatments for high-risk adult solid tumor cancers, such as head and neck, breast, pancreatic, liver, and colorectal cancers.

Different formulations of cGMP RBD are also undergoing preclinical study as potential treatments for multi-drug resistant (MDR) bacteria, such as Gram-negative bacteria.

Topical formulations of cGMP RBD are also undergoing preclinical study as potential treatments for diseases of the eye, such as infectious keratitis

Tumor Cell Lysosomes as the Seminal Cancer Drug Target

Lysosomes are the central organelles for intracellular degradation of biological materials, and nearly all types of eukaryotic cells have them. Discovered by Christian de Duve, MD in 1955, lysosomes are linked to several biological processes, including cell death and immune response. In 1959, de Duve described them as ‘suicide bags’ because their rupture causes cell death and tissue autolysis. He was awarded the Nobel Prize in 1974 for discovering and characterizing lysosomes, which are also linked to each of the three primary cell death pathways: apoptosis, autophagy, and necrosis.

Building on the Discovery, Exploration, and Characterization of Lysosomes

Cancer cells, particularly advanced cancer cells, are very dependent on effective lysosomal functioning.10 Cancer progression and metastasis are associated with lysosomal compartment changes11,12, which are closely correlated (among other things) with invasive growth, angiogenesis, and drug resistance13.

RBD selectively accumulates in the lysosomes of cancer cells upon contact, disrupting the lysosomes and causing the cells to die. Provectus2,14, external collaborators5, and other researchers15,16,17 have independently shown that RBD triggers each of the three primary cell death pathways: apoptosis, autophagy, and necrosis.

Cancer Cell Autolytic Death via RBD: RBD-induced autolytic cell death, or death by self-digestion, in Hepa1-6 murine hepatocellular carcinoma (HCC) cells can be viewed in this Provectus video of the process (ethidium homodimer 1 [ED-1] stains DNA, but is excluded from intact nuclei; lysosensor green [LSG] stains intact lysosomes; the video is provided in 30-second frames, with a duration of approximately one hour). Exposure to RBD triggers the disruption of lysosomes, followed by nucleus failure and autolytic cell death. Identical responses have been shown by the Company in HTB-133 human breast carcinoma (which can be viewed in this Provectus video of the process, with a duration of approximately two hours) and H69Ar human multidrug-resistant small cell lung carcinoma. Cancer cell autolytic cell death was reproduced by research collaborators in neuroblastoma cells to show that lysosomes are disrupted upon exposure to RBD.5

Tumor Autolytic Death via RBD: RBD causes acute autolytic destruction of injected tumors (via autolytic cell death), mediating the release of danger-associated molecular pattern molecules (DAMPs) and tumor antigens; release of these signaling factors may initiate an immunologic cascade where local response by the innate immune system may facilitate systemic anti-tumor immunity by the adaptive immune system. The DAMP release-mediated adaptive immune response activates lymphocytes, including CD8+ T cells, CD4+ T cells, and NKT cells, based on clinical and preclinical experience in multiple tumor types. Mediated immune signaling pathways may include an effect on STING, which plays an important role in innate immunity.9

Orphan Drug Designations (ODDs)

ODD status has been granted to RBD by the U.S. Food and Drug Administration for metastatic melanoma in 2006, hepatocellular carcinoma in 2011, neuroblastoma in 2018, and ocular melanoma (including uveal melanoma) in 2019.

Intellectual Property

Provectus’ IP includes a family of US and international (a number of countries in Asia, Europe, and North America) patents that protect the process by which cGMP RBD and related halogenated xanthenes are produced, avoiding the formation of previously unknown impurities that exist in commercial-grade rose bengal in uncontrolled amounts. The requirement to control these impurities is in accordance with International Council on Harmonisation (ICH) guidelines for the manufacturing of an injectable pharmaceutical. US patent numbers are 8,530,675, 9,273,022, and 9,422,260, with expirations ranging from 2030 to 2031.

The Company’s IP also includes a family of US and international (a number of countries in Asia, Europe, and North America) patents that protect the combination of RBD and CB (e.g., anti-CTLA-4, anti-PD-1, and anti-PD-L1 agents) for the treatment of a range of solid tumor cancers. US patent numbers are 9,107,887, 9,808,524, 9,839,688, and 10,471,144, with expirations ranging from 2032 to 2035; US patent application numbers include 20200138942 (i.e., 16/678,133), which has been allowed.

Verastem Oncology Announces Conversion of Senior Notes Eliminating Substantially All Outstanding Debt

On July 10, 2021 Verastem Oncology (Nasdaq: VSTM), a biopharmaceutical company committed to advancing new medicines for patients battling cancer, reported that it has converted all of the $28.0 million aggregate principal of the Company’s 2020 5.00% Convertible Senior Notes due 2048 (the 2020 Notes) in exchange for approximately 8.6 million shares of the Company’s common stock, based on the Company’s existing Mandatory Conversion right (Press release, Verastem, JUL 19, 2021, View Source [SID1234584947]). This transaction, which eliminates substantially all of the Company’s outstanding debt, preserves approximately $31.2 million in cash, including $3.2 million in future interest payments that would have been payable through November 1, 2023.

Robert Gagnon, Chief Financial Officer of Verastem Oncology, commented: "This conversion of our 2020 Notes eliminates substantially all outstanding debt and provides us with greater financial flexibility, all while reducing future cash needs for interest payments and to repay the notes at maturity. We now enter the second half of 2021 with a stronger balance sheet and believe we are well positioned to execute on our corporate objectives, including the advancement of VS-6766 and defactinib through registration-directed Phase 2 clinical trials in low-grade serous ovarian cancer (LGSOC) and KRAS G12V-mutant non-small cell lung cancer (NSCLC)."

On November 6, 2020, the Company entered into a privately negotiated agreement with an investor who held the Company’s 2018 5.00% Convertible Senior Notes due 2048 (the 2018 Notes), and exchanged approximately $28.0 million aggregate principal amount of the 2018 Notes for approximately $28.0 million aggregate principal amount of newly issued 2020 Notes. Under the terms of the 2020 Notes, Verastem became eligible to exercise its right to cause all outstanding 2020 Notes to be converted automatically because the daily volume weighted average price (VWAP) per share of the Company’s common stock was equal to or exceeded 123.08% of the conversion price on each of at least 20 VWAP trading days during a 30 consecutive VWAP trading day period. The conversion rate for the 2020 Notes was 307.6923 shares of the Company’s common stock per $1,000 principal amount of the 2020 Notes, which is equivalent to a conversion price of approximately $3.25 per share, representing an approximately 153.9% premium to the sale price of $1.28 per share of the Company’s common stock on November 5, 2020.

Verastem Oncology ended the first quarter 2021 with cash, cash equivalents and investments of $127.1 million. With the anticipated proceeds from the sale of COPIKTRA, the Company expects that it will have a cash runway until at least 2024 to deliver on the current programs for VS-6766 and defactinib, including clinical and regulatory milestones and development in LGSOC and KRAS mutant NSCLC.