On September 4, 2019 Vermillion, Inc. (Nasdaq: VRML), a bioanalytical-based women’s health company focused on gynecologic disease, reported the publication of two independent studies demonstrating that OVA1 (Blood Multivariate Index Assay (MIA) for Ovarian Cancer Risk Assessment) improves ovarian cancer risk detection in women compared to alternative technology, such as CA125 and CA125 & HE4 (Risk of Malignancy Algorithm ROMA) (Press release, Vermillion, SEP 4, 2019, View Source [SID1234539277]). With more than 80% of ovarian cancer being diagnosed in late stages1,2, these data support the National Ovarian Cancer Coalition’s mission for Ovarian Cancer Awareness Month, of earlier recognition of symptoms and earlier detection.2

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The studies specifically demonstrate that OVA1 is markedly more sensitive in ovarian cancer detection in African-American women 79.2% for OVA1, vs. 33.3% compared to CA1253, and 79.1% v. 54.5% compared to CA125 plus HE4 (Risk of Malignancy Algorithm ROMA), when using the American College of Obstetricians and Gynecologists (ACOG) cutoff >200 CA125 U/ml3 for premenopausal women. In addition, even applying a more conservative 2007 cutoff for premenopausal women (CA125 >67 U/ml, Dearking 2007)4, OVA1 still outperformed CA125 whose sensitivity was only 62.5%.

"Recent studies have shown that African American women have lower CA125 levels than other ethnicities which could lead to under diagnosis of cancer in that population. Our results from the two new studies demonstrate that OVA1 is clearly superior to CA-125, as well as to ROMA, in ovarian cancer risk detection for women with pelvic masses, particularly in African American women" said Charles Dunton, M.D., Global Medical Director of Vermillion, and lead author. "By giving more women greater access to a better risk detection method, we can help correct the disparity in care offered to African-American women, who generally have poorer survival rates from ovarian cancer and currently face a greater risk of cancer not being detected."

Key takeaways from the studies:

"Multivariate Index Assay Outperforms CA125 in Detection of Ovarian Malignancy in African American Women" authored by Dunton et al was published in Future Oncology; Published Online: Aug 2019; View Source

OVA1 (MIA) in African American women is more sensitive than CA125; 79.2% v 33.3% (2007 ACOG)3 v 62.5% (2007 Dearking)4
OVA1 (MIA) in Caucasian women is more sensitive than CA125, 93.2% v 80.4%
"Multivariate Index Assay is Superior to CA125 and HE4 Testing in Detection of Ovarian Malignancy in African American Women" authored by Dunton et al, was published in Biomarkers in Cancer 11:1-4, 2019

OVA1(MIA) in African American women is more sensitive than ROMA: 79.1% v 54.5%
OVA1(MIA) in Caucasian women is more sensitive than ROMA: 93.2% v 82.9%
"This is very interesting data. This sort of research is critical to understand tumor marker and OVA1 (MIA) differences in race and ethnicity", said Barbara Goff, MD. Professor and Chair of Obstetrics and Gynecology and affiliated researcher at the Fred Hutchinson Cancer Research Center, University of Washington School of Medicine. "It is so critically important to investigate the sensitivity of such detection methods based on the inherent differences in individual populations. This preliminary research points to a substantial step in the right direction."

OVA1 is an FDA-cleared and ACOG endorsed blood test offered via ASPIRA Labs, Vermillion’s wholly owned subsidiary. OVA1 proactively assesses the risk of ovarian malignancy from a simple blood test, as a pre-operative biopsy is not medically appropriate. Clinically, OVA1 objectively guides the patient treatment care plan for low risk and high-risk pelvic mass patients.

"Disparity in care continues to be a major global problem, and particularly for cancer risk detection and treatment for underserved women," said Valerie Palmieri, President, and CEO of Vermillion, Inc. "We are proud that OVA1 is demonstrated to accurately identify more patients, especially African-American women, and help ensure that they get the proper treatment. We will continue to work to support the goals of Ovarian Cancer Awareness Month and give ALL women of every socioeconomic background access to the best possible methods of cancer risk detection."

On September 4, 2019 Vaxart, Inc., a clinical-stage biotechnology company developing oral recombinant vaccines that are administered by tablet rather than by injection, reported that Wouter Latour, M.D., president and chief executive officer of Vaxart, will present a company update and overview at the H.C. Wainwright 21st Annual Global Investment Conference on Tuesday, September 10, 2019, at 12:30 p.m. EST in New York (Press release, Vaxart, SEP 4, 2019, View Source [SID1234539276]).

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A live webcast of the presentation will be available in the Investors section of Vaxart’s website at investors.vaxart.com. A replay of the webcast will be archived on Vaxart’s website for 30 days following the presentation.

On September 4, 2019 IMV Inc. (Nasdaq: IMV; TSX: IMV), a clinical-stage immuno-oncology company, reported a collaboration with The Wistar Institute and Meenhard Herlyn, D.V.M., D.Sc., professor in the Molecular and Cellular Oncogenesis Program and director of Wistar’s Melanoma Research Center (Press release, IMV, SEP 4, 2019, View Source [SID1234539275]).

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Under this collaboration, IMV and The Wistar Institute will partner to develop a targeted T cell therapy against the common BRAF cancer mutation, based on peptides identified by the Herlyn lab. Mutations in this gene are the most frequently identified cancer-causing mutations in melanoma and have been identified in various other cancers, including non-Hodgkin lymphoma, colorectal cancer, thyroid cancer, and non-small cell lung and ovarian carcinomas1.

"We are pleased to initiate this collaboration with The Wistar Institute, a world leader in biomedical research and early-stage discovery science with highly relevant expertise to our shared goals in the development of novel treatments for cancer. In particular, Dr. Herlyn has transformed the scientific understanding of stem cells as they relate to cancer and his work in melanoma serves as the basis for numerous therapies now in clinical trials or recently approved," said Frederic Ors, IMV’s Chief Executive Officer. "We believe that cancer-driving mutations, like BRAF, which are directly involved in malignant processes and do not easily escape the immune system, represent an exciting new avenue for targeted T cell therapies. We look forward to working with Dr. Herlyn and his team, leveraging our DPX platform to explore the therapeutic potential of this target in melanoma and other cancers."

"Small-molecule inhibitors of BRAF have shown to be very effective targeted cancer therapies, but with limited long-term benefit due to the onset of therapy resistance. Alternative strategies with emerging therapeutic approaches are needed for the successful long-term treatment of cancers with the BRAF mutation," said Dr. Herlyn. "Immunotherapy could provide a more effective mechanism to target these mutations and we are excited to collaborate with IMV, as its DPX technology enables us to develop targeted T cell therapies aimed at BRAF to test and validate this important hypothesis."

The project scope includes optimizing the DPX formulation with the BRAF peptides and testing the investigational T cell therapy in the pioneering pre-clinical research models at Wistar. As part of the collaboration agreement, IMV holds an exclusive option to in-license intellectual property related to the program.

On September 4, 2019 Tiziana Life Sciences plc (NASDAQ: TLSA), a biotechnology company focusing on the discovery and development of innovative therapeutics for inflammation and oncology indications, reported additional positive Phase 2a clinical data exhibiting impressive clinical activity of Milciclib monotherapy in patients with advanced Sorafenib-resistant or -intolerant patients with unresectable or metastatic hepatocellular carcinoma (HCC) (Press release, Tiziana Life Sciences, SEP 4, 2019, View Source [SID1234539274]).

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This Phase 2a multi-center, single-arm, repeated-dose (100 mg once daily; 4 days on/3 days off for 4 weeks; defining each cycle) and 6-month duration study was conducted to evaluate the safety, tolerability and anti-tumor activity of Milciclib in Sorafenib-resistant patients with unresectable or metastatic advanced HCC. The trial enrolled 31 patients in Italy, Greece and Israel, of which 28 patients were evaluable. While the primary endpoint of this study was overall safety, secondary endpoints were also evaluated.

As previously announced on 22 July 2019, the clinical data from the Phase 2a trial indicated that Milciclib was well tolerated with manageable toxicities and no recorded drug related deaths, thereby meeting the trial’s primary endpoint. The Company now announces all the major highlights of the clinical data from the trial, which also indicate positive clinical activity relating to the secondary endpoints including progression-free survival ("PFS") and time to progression ("TTP").

MAJOR HIGHLIGHTS OF THE CLINICAL DATA

As per the study protocol, data collection was limited to 6-months. Thus, clinical data were not collected from patients under compassionate use treatment. The clinical activity assessment in evaluable patients was based on the investigators’ review using the modified Response Evaluation Criteria in Solid Tumors (mRECIST).

14 out of 28 (50%) evaluable patients completed 6-month duration of the trial.
9 out of 14 patients (64.2%) were approved by their respective ethical committees to continue the treatment.
5 of the 9 patients on compassionate use had received Milciclib for a total of 9, 9, 11, 13 and 16 months.
As of 1 September 2019, the remaining 4 patients continuing the treatment are in their 10th, 11th, 11th and 12th months.
Both median TTP and PFS were 5.9 months (95% Confidence Interval ("CI") 1.5-6.7 months) out of the 6-months duration of the trial.
17 of 28 (60.7%) evaluable patients showed ‘Stable Disease’ (SD; met at least once in an 8-week interval).
One patient (3.6%) showed ‘Partial Response’ (PR).
18 of 28 (64.3%) evaluable patients showed ‘Clinical Benefit Rate’ defined as CBR=CR+PR+SD (with CR representing Complete Remission).
Sorafenib (Bayer) was approved, based on the clinical data from the pivotal Phase 3 (SHARP) clinical trial1, as the first line therapy for naive HCC patients. The clinical data from that study showed median TTP of 5.5 months (95% CI 4.1-6.9 months), CBR of 43% and 71% SD by RECIST criteria1. Conversely, the clinical data from a phase 2 trial with Sorafenib in patients with advanced HCC, showed SD (33.6%), TTP of 4.2 months and median OS of 9.2 months2.

Regorafenib was approved, based on the clinical data from the pivotal Phase 3 (RESORCE) clinical trial3, as the second line therapy for sorafenib-resistant HCC patients. In this study, Regorafenib showed median PFS of 3.1 months (95% CI 2.8-4.2 months), median TTP of 3.2 months (95% CI 2.9-4.2 months) and disease control rate (DCR, similar to CBR) of 65% by mRECIST. On the other hand, the clinical data from a Phase 2 study in patients with intermediate and advanced HCC, Regorafenib showed median TTP of 4.3 months (95% CI 2.9-13.1 months), SD (69%) and PR was 3%4.

"The current therapies for HCC are often associated with severe toxicities, resulting in poor patient compliance. Hence, there is an immediate need for efficacious therapies that will not compromise patients’ quality of life. We believe that the overall safety profile of Milciclib is an important competitive advantage over existing therapies currently used for treating HCC" said Gabriele Cerrone, Chairman and founder of Tiziana Life Sciences.

"The positive clinical activity and tolerability data of Milciclib in Sorafenib-resistant and advanced HCC patients are very encouraging and provides affirmation for continued development of Milciclib, either as monotherapy or combination therapy" said Dr. Kunwar Shailubhai, CEO & CSO of Tiziana. "We reported last year at AASLD that Milciclib produced pronounced synergistic anti-HCC activity in combination with any one of the FDA approved tyrosine kinase inhibitor (TKI) class of drugs, including Sorafenib (Nexavar), Regorafenib (Stivarga), and Lenvatinib (Lenvima)5. Thus, we believe that Milciclib in combination with any one of the TKI drugs has good potential to expand the Clinical Benefit Rate in HCC patients."

Cited References

1. Llovet, J., Ricci, S., Mazzaferro, V., Hilgard, P., Gane, E., Blanc, J-F., de Oliveira, A., Santoro, A., Raoul, J-L, Forner, A., Schwartz, M., Porta, C., Zeuzem, S., Bolondi, L., Greten, T., Galle, P., Seitz, J-F., Borbatch, I., Haussinger, D., Giannaris, T., Shan, M., Moscovici, M., Voliotiz, D., and J. Bruix. (2008) Sorafenib in Advance Hepatocellular Carcinoma. N Engl. J Med. 359:378.

2. Abou-Alfa, G., Schwartz, L., Ricci., S., Amadori, D., Santoro, A., Figer, A. De Greve, J., Douillard, J-Y., Lathia, C., Schwartz, B., Taylor, I., Moscovici, M. and L. Saltz. (2006). Phase II Study of Sorafenib in Patients with Advanced Hepatocellular Carcinoma. J. Clin. Oncol. 24:4293.

3. Bruix, J, Qin, S., Merle, P., Granito, A., Huang, Y-H, Bodoky, G., Pracht, M., Yokosuka, O., Rosmorduc, O., Breder, V., Gerolami, R., Masi, G., Ross, P., Song, T., Bronowicki, J-P., Ollivier-Hourmand, I., Kudo, M., Cheng, A-L., Llovet, J.M., Finn, R., LeBerre, M-A., Baumhauer, A., Meinhardt, G. and Han, G. (2017) Regorafenib for patients with hepatocellular carcinoma who progressed on sorafenib treatment (RESORCE): a randomized, double-blind, placebo-controlled, phase 3 trial. Lancet 389: 56.

4. Bruix, J., Tak, W-Y., Gasbarrini, A., Santoro, A., Colombo, M., Lim, H-Y., Mazzaferro, V., Wiest, R., Reig, M., Wagner, A., and Bolondi, L.(2013) Regorafenib as Second-Line Therapy for Intermediate or Advanced Hepatocellular Carcinoma: Multicentre, Open-Label Phase II Safety Study. Eur.J. Cancer 49:3412.

5. Jindal, A., Palejwala, V. and Shailubhai, K. (2018). Oral treatment with milciclib either alone or in combination with sorafenib inhibited tumor growth in an orthotopic model of hepatocellular carcinoma. Hepatology 68 Number 1 (Suppl): 879A (Abstract 1543)

The person who arranged for the release of this announcement on behalf of the Company was Dr Kunwar Shailubhai, CEO & CSO of Tiziana.

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On September 4, 2019 Ribon Therapeutics, a biotechnology company developing first-in-class therapeutics targeting novel enzyme families activated under cellular stress conditions, reported the dosing of the first patient in its Phase 1 clinical trial of RBN-2397, the company’s first-in-class PARP7 inhibitor (Press release, Ribon Therapeutics, SEP 4, 2019, View Source [SID1234539273]). PARP7 belongs to a family of enzymes activated under cellular stress conditions, known as monoPARPs, which are distinct from polyPARPs such as PARP1/2. Recent science pioneered by Ribon has shown monoPARPs are key regulators of stress responses and are linked to the development of certain diseases, including cancers. The Phase 1 trial of RBN-2397 is the first-ever clinical evaluation of a monoPARP inhibitor.

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"With RBN-2397, we are targeting PARP7, which plays a critical role in cancer cell survival. Inhibiting PARP7 has been shown to potently inhibit cancer cell proliferation and also release a ‘brake’ that cancer cells use to evade the immune system," said Sudha Parasuraman, M.D., Chief Medical Officer, Ribon Therapeutics. "We have seen very strong preclinical evidence supporting the clinical potential of RBN-2397, and we believe it can become a valuable new treatment option for cancer patients."

"Bringing our lead compound into the clinic is a key milestone for Ribon, demonstrating our ability to advance from program initiation to the clinic in under three years," said Victoria Richon, Ph.D., President and Chief Executive Officer, Ribon Therapeutics. "This progress validates the utility and efficiency of our platform in rapidly interrogating novel biological pathways and developing clinical drug candidates. The platform has broad potential applications, enabling us to develop first-in-class therapeutics against an expanding set of novel targets in oncology, neurodegeneration and inflammatory disease."

The Phase 1 clinical trial is a multi-center, open-label, dose-escalation study designed to assess the safety, tolerability, and pharmacokinetics of RBN-2397, as well as initial signs of anti-tumor activity in patients with advanced-stage solid tumors. The goals of the study are to establish the recommended dose for future clinical investigation and to explore pharmacodynamic readouts and predictive biomarkers. The study is comprised of a dose escalation phase, which will be followed by a number of expansion cohorts evaluating RBN-2397 in patients with various tumor types, including squamous cell carcinoma of the lung, in which PARP7 has been shown to be genetically amplified. Additional information on this clinical trial can be found on www.clinicaltrials.gov.

RBN-2397 – Inhibiting PARP7, a Key monoPARP Cancer Dependency

Ribon’s lead program, RBN-2397, is focused on inhibiting overactive PARP7 in tumors, which has been shown to play a key role in cancer survival. Ribon’s research has discovered that many cancer cells rely on PARP7 for intrinsic cell survival, and that PARP7 allows cancer cells to "hide" from the immune system. Ribon has demonstrated that inhibition of PARP7 with RBN-2397 can potently inhibit the growth of cancer cells and restore interferon signaling, effectively releasing the "brake" cancer uses to hide from the immune system and suppress both innate and adaptive immune mechanisms. In several cancer models, RBN-2397 demonstrated durable tumor growth inhibition, potent antiproliferative activity and restoration of interferon signaling. Ribon plans to initially develop RBN-2397 in squamous cell carcinoma of the lung, where research has shown PARP7 to be genetically amplified. The company also plans to explore RBN-2397 for the treatment of additional cancers, including cancers of the aerodigestive tract, pancreatic cancer and ovarian cancer.

PARP7 is a member of the monoPARP family of proteins, which are key regulators of stress responses that enable cancer cells to survive and also evade immune detection, and emerging science has linked their activity with disease development. MonoPARPs are a family of 12 enzymes that are functionally and structurally distinct from the more well-known polyPARPs, such as PARP1/2. MonoPARPs function across a variety of stress responses relevant to disease development in cancer, inflammatory conditions and neurodegenerative diseases. Ribon has built an integrated technology platform to interrogate monoPARPs to develop first-in-class, small molecule therapeutics.