On June 24, 2021 PharmaCyte Biotech, Inc. (OTCQB: PMCB), a biotechnology company focused on developing cellular therapies for cancer and diabetes using its signature live-cell encapsulation technology, Cell-in-a-Box , reported the efforts being undertaken by the Company to have the U.S. Food and Drug Administration (FDA) clinical hold lifted (Press release, PharmaCyte Biotech, JUN 24, 2021, View Source [SID1234584329]). These efforts are necessary so that PharmaCyte may proceed with its planned clinical trial in locally advanced, inoperable, pancreatic cancer (LAPC).

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The Company’s Chief Executive Officer, Kenneth L. Waggoner, discussed the background of the clinical hold stating, "On September 1, 2020, the Company submitted an Investigational New Drug Application (IND) to the FDA for our planned Phase 2b clinical trial in LAPC. On October 1, 2020, the Company received notice from the FDA that it had placed our IND on clinical hold. And on October 30, 2020, the FDA sent a letter to us setting forth the reasons for the clinical hold and specific guidance on what we must do to have the clinical hold lifted."

For the purpose of addressing the clinical hold, the Company has assembled a team of regulatory and scientific experts to respond to the items requested by the FDA. That team has been actively working to complete the list of items requested by the FDA. Those items can be found on pages 28 and 29 of PharmaCyte’s latest Form 10-Q for the period ending January 31, 2021.

Mr. Waggoner then explained, "The Company is in varying stages of addressing the studies and acquiring the information requested by the FDA to have the clinical hold lifted. Thus far:

The Company has successfully completed a 3, 6, 9, and 12-month product stability study on the Company’s clinical trial product (CypCaps), including container closure integrity testing for certain timepoints; the next time point in this ongoing study will be at 18 months of product stability.
The Company has designed and commenced various additional studies recommended by the FDA, including a stability study on the cells from the Master Cell Bank (MCB) used to make the CypCaps, which are already at the 3-year stability timepoint, and further sequence analysis of the DNA encoding of the Cyp2B1 gene in the encapsulated cells in the CypCaps. It has also collated existing information on the reproducibility and quality of the filling of the MCB cells into vials ready for CypCaps manufacturing as requested by the FDA.
The Company has designed and commenced biocompatibility studies such as (i) a Subchronic and Chronic Toxicity study; (ii) a Skin Sensitization study; (iii) an Acute Systematic Toxicity study; (iv) an Ames test [Genotoxicity Bacteria and Reverse Mutation tests]; (v) an Intracutaneous test; (vi) a Complement Activation test; (vii) a Hemolysis test; (viii) an In Vitro Cytotoxicity test; and (ix) an In Vivo Micronucleus assay. To enable these tests to be performed, the Company has already manufactured and delivered an additional 400 syringes of empty capsules. Some of the data being generated will also be used to demonstrate comparability with the CypCaps successfully used—in two earlier German clinical trials for pancreatic cancer.
The Company has designed and commenced studies designed to show that CypCaps are not in any way adversely affected by the catheters used by interventional radiologists to deliver them, nor by the contract media used to visualize the blood vessels during implantation of the CypCaps. Further, the studies are designed to demonstrate how robust the CypCaps are during delivery and use as well as to document that the syringes used to deliver the CypCaps will allow delivery consistently, smoothly and safely.
Austrianova is providing additional detailed confidential information to the FDA on the manufacturing process, including information on the improvements made to the product since the last clinical trials with respect to reproducibility and safety, but that have not changed the overall physical characteristics of the CypCaps. The Company is supporting Austrianova in this work.
The Company is in the process of updating its documentation to include (i) more pre-clinical data as discussed above, (ii) some additional parameters for release of the CypCaps, (iii) specifically recommending the catheters and contrast used to deliver the CypCaps as well as (iv) extending its discussion on immunology.
Finally, the Company has designed an abbreviated study in pigs to address biocompatibility and long-term implantation of the capsules. This animal study will complement the positive data already available from the previous human clinical trials showing the safety of CypCaps implantation for up to two years in humans.
The Company feels that the carcinogenicity data obtained to date, together with the long-term data from the two previous German trials, show that CypCaps are unlikely to cause any long-term cancer. Furthermore, the patients who will be treated with CypCaps are already suffering with inoperable, late-stage pancreatic cancer, and chemotherapeutics, like ifosfamide, (the drug given at low concentrations with the CypCaps), are approved for treatment of cancer even through it is known to have a carcinogenic potential. Indeed, virtually all anti-cancer treatments used today by their very nature have an inherent potential to cause cancer. Moreover, the cells within the CypCaps are primed by ifosfamide to commit cell suicide if they try to divide."
Mr. Waggoner continued, "The list of items that we have been addressing is lengthy, time consuming and costly. Some of the studies required by the FDA caused us to find suitable partners and Contract Research Organizations to assist us in the work. But our team has been working tirelessly on every item and will continue to do so until we have done all that we can to satisfy the FDA requests. In addition, we plan to request a meeting with the FDA for further guidance and to update them on the progress that we have made.

"As we continue to reach milestones on the requested studies, we will strive to report on the material developments that we believe will allow us to get the clinical hold lifted."

To learn more about PharmaCyte’s pancreatic cancer therapy and how it works inside the body to treat locally advanced inoperable pancreatic cancer, we encourage you to watch PharmaCyte’s documentary video complete with medical animations at: View Source

On June 24, 2021 Prothena Corporation plc (NASDAQ:PRTA), a late-stage clinical company with a robust pipeline of novel investigational therapeutics built on protein dysregulation expertise, reported that Bristol Myers Squibb exercised its option under the global neuroscience research and development collaboration to enter into an exclusive U.S. license for PRX005 and will pay Prothena $80 million (Press release, Prothena, JUN 24, 2021, View Source [SID1234584328]). PRX005 is designed to be a best-in-class anti-tau antibody by specifically targeting an area within the microtubule binding region (MTBR) for the potential treatment of Alzheimer’s disease (AD). Phase 1 study with PRX005 has initiated.

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"Our continued collaboration with Bristol Myers Squibb on PRX005 allows us to further leverage our combined expertise to accelerate the development of therapies with the potential to transform the lives of those affected by neurodegeneration," said Gene Kinney, PhD, President and Chief Executive Officer of Prothena. "Mounting scientific evidence suggests the MTBR of tau is most closely associated with the pathogenic spread of tau. The presence of MTBR fragments in cerebrospinal fluid have also been shown to correlate with dementia stages in Alzheimer’s disease to a higher degree than fragments of other tau regions. These recent biological understandings support the further development of PRX005, which uniquely targets a key region within the MTBR of the tau protein. In our studies, we have found that targeting specific regions within the MTBR reduce pathogenic tau uptake into neurons, an attribute that was not achievable with antibodies targeting other regions of tau."

"We are pleased that our collaboration with Prothena has successfully identified and developed PRX005, a novel, differentiated anti-tau antibody that we believe has the potential to provide a meaningful disease modifying treatment option for the millions of patients that suffer from Alzheimer’s disease," said Richard Hargreaves, Senior Vice President and Head of Bristol Myers Squibb’s Neuroscience Thematic Research Center. "We look forward to our continued partnership with Prothena."

Tau is a microtubule associated protein, which aggregates and hyper-phospohrylates in the brains of individuals with AD to form pathological neurofibrillary tangles. Tau tangles, along with amyloid beta plaques represent the pathological hallmarks of AD. The presence of tau pathology strongly correlates with neurodegeneration and cognitive impairment in AD and its pattern of progression throughout the brain suggests that tau pathology spreads through anatomically connected pathways via cell-to-cell transmission, a hypothesis supported by multiple preclinical studies. This propagation of pathology is thought to be mediated by tau "seeds" containing the MTBR of tau. PRX005 has demonstrated superior ability to bind, intercept and block cellular internalization of pathogenic tau, and mitigate downstream neurotoxicity compared to other anti-tau antibodies in multiple preclinical studies.

About the Global Neuroscience Research and Development Collaboration

This global neuroscience research and development collaboration is focused on three proteins implicated in the pathogenesis of several neurodegenerative diseases, including tau, TDP-43 and an undisclosed target. PRX005 is designed to be a best-in-class anti-tau, MTBR-specific antibody for the potential treatment of Alzheimer’s disease and is the first program to advance to the clinic from this collaboration, where the Phase 1 study has initiated. With this payment, Prothena will have received a total of $230 million pursuant to the collaboration, and is eligible to receive up to an additional $160 million for U.S. rights, up to $165 million for global rights, and up to $1.7 billion for regulatory and commercial milestone payments for a total of up to $2.2 billion plus potential tiered commercial sales royalties across multiple programs.

About PRX005 for Alzheimer’s Disease

PRX005 is designed to be a best-in-class anti-tau antibody that specifically targets a key region within the microtubule binding region (MTBR), which has been shown in preclinical studies to be involved in the pathological spread of tau. Neurofibrillary tangles composed of misfolded tau proteins, along with amyloid beta plaques, are pathological hallmarks of Alzheimer’s disease (AD). Cell-to-cell transmission of pathogenic extracellular tau and the accumulation of pathogenic tau also correlate with the progression of symptomatology and clinical decline in patients with AD. Recent publications suggest that during the course of AD progression, tau appears to spread throughout the brain via synaptically-connected pathways; this propagation of pathology is thought to be mediated by tau "seeds" containing the MTBR of tau. Additionally, it has been recently reported that the presence of MTBR fragments in cerebrospinal fluid correlate with dementia stages in AD to a higher degree than fragments of other tau regions. In preclinical research, antibodies targeting this region of tau were superior in blocking tau uptake and neurotoxicity, which has been associated with efficacy in AD animal models. In these preclinical models, PRX005 demonstrated significant inhibition of cell-to-cell transmission and neuronal internalization in vitro and in vivo and slowed pathological progression in a tau transgenic mouse model.

About Alzheimer’s Disease

Alzheimer’s disease is a type of dementia that can cause increasingly serious symptoms, including confusion, disorientation, mood and behavioral changes, difficulty speaking, swallowing, and walking. Approximately 6.2 million Americans age 65 and older are currently estimated to be living with Alzheimer’s disease, making it the most common neurodegenerative disorder. It is also the sixth leading cause of death among adults in the United States. There is an urgent need for therapies that slow the progression and ultimately prevent Alzheimer’s disease to address this global healthcare crisis. Prothena’s Alzheimer’s disease portfolio spans next generation antibody immunotherapy, small molecule and vaccine approaches, geared toward building upon first generation treatments to advance the treatment paradigm.

On June 24, 2021 Starpharma (ASX: SPL, OTCQX: SPHRY) reported that a presentation by Dr Jackie Fairley, CEO, reported that it will be broadcast on Thursday 24 June 2021 (US ET) as part of OTCQX’s Virtual Life Sciences Investor Forum (Press release, Starpharma, JUN 24, 2021, View Source;mc_eid=bf52dd3418 [SID1234584327]). The Life Sciences Investor Forum is a leading investor conference that is attended by tens of thousands of investors, primarily US-based retail investors, as well as advisors.

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Details of the forum are found via this link: Virtual Life Sciences Investor Forum. Starpharma’s pre-recorded presentation features a company overview, including the latest updates on the VIRALEZE Antiviral Nasal Spray which has shown potent antiviral activity against multiple variants of coronavirus/SARS-CoV-2 in laboratory studies, and has been registered in Europe (launched) and India. The presentation will also include an overview of Starpharma’s DEP clinical-stage and preclinical assets, and corporate partnerships for its DEP drug delivery platform, including with Merck & Co., Inc (MSD) and AstraZeneca, as well as its VivaGel products, which are approved in more than 45 countries. The presentation is attached and also available on Starpharma’s website.

On June 24, 2021 Sirnaomics, Inc., a biopharmaceutical company engaged in the discovery and development of RNAi therapeutics against cancer and fibrotic diseases, reported that dose administration for the first patient in a Phase 1 U.S. clinical study for liver cancer treatment, with the company’s siRNA (small interfering RNA) drug candidate, STP705 (Press release, Sirnaomics, JUN 24, 2021, View Source [SID1234584326]). STP705 takes advantage of a dual-targeted inhibitory property and polypeptide nanoparticle (PNP)-enhanced delivery to directly knock down both TGF-β1 and COX-2 gene expression.

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This Phase 1 trial is a multicenter, open-Label, dose escalation and dose expansion study to evaluate the safety, tolerability, pharmacokinetics, and anti-tumor activity of STP705, with an intratumoral administration. In this "basket study" of up to 50 subjects suffering from cholangiocarcinoma, hepatocellular carcinoma, or liver metastases from colorectal cancer, the patients with advanced/metastatic or surgically unresectable solid tumors and are refractory to standard therapy will be treated with STP705. This therapeutic regimen is designed to take advantage of a dual-targeted inhibitory property of siRNAs and polypeptide nanoparticle (PNP)-enhanced delivery to directly knock down both TGF-β1 and COX-2 gene expressions. Early pre-clinical and clinical studies using STP705 have shown an increase of active T cell infiltration into the tumor microenvironment. In addition, knocking down TGF-β1 and COX-2 gene expressions in animal fibrosis tissue can activate fibroblast apoptosis with significant antifibrotic efficacy.

"Advancing STP705 from skin cancer to liver cancer is a major milestone for Sirnaomics’ clinical programs, especially with a basket study design that consists of multiple tumor types. We are particularly interested in learning whether the mechanism of action validated in the skin cancer clinical study can be further verified in this liver cancer study," said Patrick Lu, Ph.D., founder, President and Chief Executive Officer of Sirnaomics. "We are expecting that the combination of anti-fibrotic effects and enhanced tumor immunity will provide a novel approach for the treatment of cholangiocarcinoma and hepatocellular carcinoma using our novel siRNA therapeutics. Sirnaomics is committed to advancing our polypeptide nanoparticle delivery system for innovative RNAi-based cancer therapy."

"Liver cancer is a devastating disease for patients with high mortality and high unmet medical need," stated Michael Molyneaux, MD, Chief Medical Officer of Sirnaomics. "The company is excited to announce first dosing, as we hope to gain important insight into the potential safety and efficacy of STP705 in this Phase 1 trial and build on the data from this study to expand into other oncology indications."

Sirnaomics expects to report initial clinical data from the Phase 1 trial in the second half of 2021. Additional information about this clinical trial is available at clinicaltrials.gov using the identifier: NCT04676633

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About Liver Cancer

Liver cancer is a global health problem, with liver neoplasms representing the second-most frequent cause of cancer-related death. There are many different types of liver cancers including hepatocellular carcinoma (HCC), cholangiocarcinoma (CCA), liver angiosarcoma, hepatoblastoma and others. Additionally, liver is a highly metastasis-permissive organ. It is the most frequently afflicted organ by metastasis and liver metastases are much more common than primary hepatic tumors. The distinctive biology of the liver renders it intrinsically susceptible to metastases. The true prevalence of liver metastasis is unknown, but between 30% and 70% of patients dying of cancer have liver metastases and most patients with liver metastases will die of their disease.

STP705 and Liver Cancer

Over expressions of TGF-β1 and COX-2 have been well-characterized as playing key regulatory roles in tumorigenesis. TGF-β is produced by different liver cells and is demonstrated to induce tumor cell migration and survival. TGF-β has been found to be overexpressed in metastatic HCC tissues. Overexpression of TGF-β is generally accepted to be associated with metastasis and poor prognosis. COX-2 is reported to be highly expressed in cancer stem cells and promotes cell migration in HCC cell lines. Additionally, inhibition of COX-2 suppresses cell migration and induces apoptosis. As such TGF-β1 and COX-2 are excellent therapeutic targets for treatment of liver cancer.

STP705 is composed of two siRNA oligonucleotides targeting TGF-β1 and COX-2 mRNA respectively and formulated in nanoparticles with a proprietary Histidine-Lysine Co-Polymer (HKP) peptide. Each individual siRNA has demonstrated the ability to inhibit the expression of their target mRNA and combining the two siRNAs produces a synergistic effect that diminishes pro-fibrogenic, pro-inflammatory, and pro-tumorigenic factors. Sirnaomics has completed several pre-clinical studies that demonstrate that inhibition of TGF-β1 and COX-2 is expected to result in the inhibition of tumor growth and provide an alternative approach for the treatment of various liver cancers. Molecular analyses of the effects of administering the combination demonstrated that the inhibition of these targets had effects on downstream gene products associated with numerous oncology targets.

Additional immunohistochemistry and image analyses of the liver and tumor tissues demonstrated that animals treated with STP705 resulted in increased CD4+ and CD8+ T cell infiltration within the tumor microenvironment. Using STP705 for treatments of hepatocellular carcinoma and cholangiocarcinoma have been designated as Orphan Drug indications by U.S. FDA. STP705 has also been evaluated in a Phase 2a clinical trial for treatment of Non-melanoma skin cancer.

On June 24, 2021 SELLAS Life Sciences Group, Inc. (NASDAQ: SLS) ("SELLAS" or the "Company"), a late-stage clinical biopharmaceutical company focused on developing novel cancer immunotherapies for a broad range of indications, reported that encouraging updated clinical data from a Phase 1 investigator-sponsored clinical trial of its lead clinical candidate, galinpepimut-S (GPS), combined with the checkpoint inhibitor nivolumab (Opdivo) in patients with macroscopic (measurable) deposits of malignant pleural mesothelioma (MPM).

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The study details are as follows:

Four evaluable male patients, aged approximately 67.3 + 4.1 (standard deviation), received GPS plus nivolumab for at least one month. Initial tumor stages were II (one patient), IIB (one patient) and IV (two patients).
All patients had the MPM epithelioid and/or sarcomatoid variant, a tumor which is universally expressing Wilms Tumor 1 (WT1), one of the most widely expressed cancer antigens, ranked by the National Cancer Institute as the top priority among cancer antigens for immunotherapy.
Patients have received and progressed with, or are refractory to, frontline pemetrexed-based chemotherapy.
Average overall survival (OS) was 35.3 + 24.0 weeks with a median OS of 35.4 weeks, while average progression-free survival (PFS) was 8.8 + 4.2 weeks with a median PFS of seven weeks, both at a median follow-up of 35.4 weeks.
The safety profile of the GPS-nivolumab combination was similar to that seen with nivolumab alone, with the addition of only low-grade, temporary local reactions at the GPS injection site, consistent with previously performed clinical studies with GPS.
With approximately 3,300 cases in the United States each year, accompanied by a rising incidence in developing countries, MPM is notoriously difficult to treat and can lead to poor clinical outcomes with respect to both overall survival and progression-free survival, especially for those patients with the sarcomatoid variant who show a median overall survival of approximately 4.0 to 5.0 months. In relapsed and refractory patients who progressed after the first line standard of care pemetrexed, a similar patient population to that in the GPS nivolumab combination trial, the common treatment regimen is vinorelbine and overall survival in those patients is reported to be between 4.5 and 6.2 months. In patients treated with other chemotherapy regimens, such as carboplatin and irinotecan, median overall survival is reported to be approximately 7.0 months.

"Considering the overall poor prognosis in this particular clinical setting, these preliminary data suggest that the combination of GPS with the PD1 inhibitor nivolumab may provide meaningful clinical benefit to patients with MPM. Surprisingly, the only sarcomatoid mesothelioma patient enrolled, who was diagnosed with Stage IV cancer, experienced a survival of 25 months and is still alive," said Angelos Stergiou, M.D., Sc.D. h.c., President and CEO, SELLAS. "Patients treated with GPS plus nivolumab combination therapy appear to be surviving significantly longer than expected. We believe that this could potentially be due to the persistence of a residual cellular immunity-mediated antitumor effect with this immunotherapy combination. Studying additional patients along with longer follow-up of existing patients will hopefully provide further clarity on these data, which we expect to review over the next six months as the study progresses."

SELLAS expects to report additional clinical and immune response data in Q4 2021, including an assessment of CD8+ and CD4+ T-cell responses to the WT1 peptide pool in the GPS mixture, as well as epitope spreading (ES) by testing for antibody presence (IgG’s) directed specifically against the full-length WT1 protein (intra-antigenic ES) and IgG’s presence against other key oncofetal antigens expressed in MPM (inter-antigenic epitope spreading).