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 Shenzhen Chipscreen Biosciences’ licensing partner, HUYABIO International (HUYABIO), reported the regulatory approval for Tucidinostat (also known as Chidamide, Epidaza , HBI-8000) monotherapy of relapsed or refractory (R/R) adult T-cell leukemia/lymphoma (ATL) by the Japanese Pharmaceuticals and Medical Devices Agency (PMDA) (Press release, Shenzhen Chipscreen Biosciences, JUN 24, 2021, View Source;huyabio-international-receives-regulatory-approval-for-chidamide-monotherapy-of-adult-t-cell-leukemialymphoma-in-japan-301319258.html [SID1234584344]).

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"Relapsed and/or refractory ATLL carries a grim prognosis with limited treatment options. Data from the registration study of Chidamide has demonstrated meaningful disease response despite the advanced stage of disease, and acceptable safety profile, to address an important unmet medical need in this patient population", said Dr. Atae Utsunomiya, honorary hospital director of Imamura General hospital in Japan.

The drug was approved based on data from a Phase 2b study that involved 23 patients with aggressive ATL in Japan. These patients, having few effective treatment options, all had advanced disease either refractory to or relapsed after receiving mogamulizumab. Chidamide 40mg orally administered twice weekly resulted in disease response in a clinically meaningful proportion of patients with an acceptable safety profile.

Dr. Lu Xianping, Chairman and President of Chipscreen said, "this is an exciting news and important milestone for our licensing partner HUYABIO International and we wish them continue success in the global development of Chidamide for several other indications".

About Chidamide (Tucidinostat as INN also known as Epidaza , HBI-8000)

Chidamide is a first-in-class/best-in-class innovative medicine targeting selectively histone deacetylases (HDAC) 1, 2, 3 and 10, which was discovered and developed originally by Shenzhen Chipscreen Biosciences in China. It has unique epigenetic immunomodulatory activities approved and launched in Chinese market for the treatment of malignant T cell lymphoma at 2014 and metastatic breast cancer at 2019. It is currently at several late stage clinic studies for several other indications in China. The product’s ex-China rights were licensed out from Chipscreen to HUYABIO at 2006. Later on, HUYABIO partnered with Meiji Seika for Japanese market.

On June 24, 2021 Monte Rosa Therapeutics reported that it is capping off a fundraising spree with a $222.3 million IPO to get two of its "molecular glue" treatments into the clinic and advance its other discovery-stage programs (Press release, Monte Rosa Therapeutics, JUN 24, 2021, View Source [SID1234584378]).

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The company raised $96 million in September 2020 to develop its drug discovery platform and expand its pipeline into diseases beyond cancer. It followed up with another $95 million six months later, ending the first quarter of 2021 with $168.4 million, according to a securities filing. Of course, drug development is an expensive business, and Monte Rosa filed in early June to raise up to $100 million in its IPO.

Despite being a preclinical biotech with much to prove, it bumped that IPO goal up to $213 million earlier this week, eventually collecting $222.3 million by offering 20% more shares than originally planned. But seeing a biotech go public without any human data isn’t unusual these days; even before the COVID-19 pandemic spurred interest and investment in the sector, companies had been hitting Wall Street at increasingly earlier stages of development.

RELATED: Monte Rosa snags $95M to speed lead ‘molecular glue’ treatment into the clinic

Molecular glues are small molecules designed to treat disease by commandeering the body’s own protein degrading process. As their name suggests, they work by sticking proteins to each other.

Monte Rosa earmarked about $47 million to $57 million for a cancer treatment that targets GSPT1, which plays a role in cancers driven by the Myc family of transcription factors. The cash should get it through a phase 1/2 study.

Beyond GSPT1, Monte Rosa will use between $120 million and $130 million to get a second program into phase 1, a third program to an IND filing and a fourth to IND-enabling studies, according to the filing. Another $65 million to $75 million will bankroll the development of its drug discovery platform.

"[Molecular glues] work by allosterically changing the receptor surface of E3 ligases to attract a protein target," said Monte Rosa CEO Markus Warmuth, M.D., referring to enzymes that tag proteins with ubiquitin for degradation by a protein complex called a proteasome, in a previous interview. "We have a singular focus on finding these molecules that reshape the surface of an E3 ligase and thereby attract otherwise undruggable targets."

RELATED: Sana snags $587.5M IPO to catapult cell therapies into the clinic

The best-known molecular glue medicines are thalidomide and its successor molecule lenalidomide—aka Bristol Myers Squibb’s blood cancer drug Revlimid—which both reshape an E3 ligase receptor called cereblon. However, this class of drugs hasn’t been hunted in a systematic way in the past, which is exactly what Monte Rosa’s technology allows it to do.

Monte Rosa isn’t alone in the protein degradation field, but it believes molecular glues can go where other approaches cannot. Other players are working on the hypothesis that eliminating disease driving proteins is a better approach than inhibiting them. They’re "redrugging the druggable," Warmuth said, developing degraders for targets that can be inhibited by traditional drugs.

Arvinas, for example, is developing drugs called proteolysis targeting chimeras, or PROTACs, to degrade the androgen and estrogen receptors, which are major drivers of prostate cancer and breast cancer, respectively. And Kymera Therapeutics is working on degraders of scaffolding kinase IRAK4 and transcription factor STAT3, both of which play a role in cancer.

Monte Rosa wants to go after targets like GSPT1 that haven’t been accessible because drug developers didn’t have the technology to handle them.

On June 24, 2021 GT Biopharma, Inc. ("GT Biopharma" or the "Company") (NASDAQ: GTBP), a clinical stage immuno-oncology company focused on developing innovative therapeutics based on the Company’s proprietary natural killer (NK) cell engager (TriKE) protein biologic technology platform, reported that GT Biopharma CEO, Tony Cataldo will be presenting as a VIP speaker at the upcoming Sir Anthony Ritossa’s Global Family Office Investment Summit in Monaco from June 30 to July 2, 2021 (Press release, GT Biopharma, JUN 24, 2021, View Source [SID1234584313]).

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The Sir Anthony Ritossa’s Global Family Office Investment Summit in Monaco is one of a series of international summits held annually as a platform for exceptional networking between Family Offices and Thought Leaders from all over the world. Summit delegations consist of prestigious family offices, private investors, sheikhs, royal families and leading businesses from 30+ countries representing more than $4.5 trillion in wealth.

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