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

On June 24, 2021 IN3BIO Research Limited reported that the company has received the Clinical Trial Application approval from the Bulgarian Drug Agency and Ethical Committee to initiate a Phase I/II clinical trial of its colorectal cancer vaccine in Bulgaria (Press release, In3Bio, JUN 24, 2021, View Source [SID1234584345]).

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IN3BIO will trial its innovative anti-EGF vaccine IN01, in combination with small molecule inhibitors (SMIs) in patients suffering from KRAS or NRAS (Cohort A) or BRAF (Cohort B) mutated colorectal cancer.

Erik D’Hondt, CEO of IN3BIO said "We are delighted to have reached this significant regulatory step to conduct our clinical trial in Bulgaria. This first approval will lead to patients being enrolled rapidly in centres in Bulgaria, then in clinical centres in other EU and non-EU countries".

About IN01

IN01 vaccine is a proprietary biologic fusion molecule designed and developed by IN3BIO. It is administered after mixing with an adjuvant Montanide ISA 51 VG ST to produce an extemporaneous water in oil emulsion (W/O) known to enhance the immune response of therapeutic vaccines.

The vaccination of IN01 produces anti-EGF antibodies which capture EGF and prevent it from binding to its target, i.e. EGF-receptor on cell surface. This prevents proliferation of tumour cells affected by EGF mediated pathways.

IN01 is manufactured in a contracted certified GMP facility in the EU. Extensive testing as a single molecule or in combination with SMIs showed no adverse effect in several pre-clinical studies.

On June 24, 2021 Boston Scientific Corporation (NYSE: BSX) reported it exercised its option to acquire the remaining shares of Farapulse, Inc (Press release, Boston Scientific, JUN 24, 2021, View Source,-Inc [SID1234584380]). The acquisition will complement the existing Boston Scientific electrophysiology portfolio to include the FARAPULSE Pulsed Field Ablation (PFA) System – a non-thermal ablation system for the treatment of atrial fibrillation (AF) and other cardiac arrhythmias .

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"The emerging field of PFA has the potential to alter the future of ablation therapy and has shown the promise of improvements in both safety of cardiac ablations for patients and efficiency and ease-of-use of these procedures for physicians," said Kenneth Stein, M.D., senior vice president and chief medical officer, Rhythm Management and Global Health Policy, Boston Scientific. "The FARAPULSE PFA System is intended to enable physicians to precisely ablate cardiac tissue while minimizing procedural complications, and real-world and clinical evidence from trials throughout Europe have demonstrated encouraging, positive results."

Boston Scientific has been an investor in Farapulse since 2014 and currently holds an equity stake of approximately 27 percent. As a result, the transaction consists of an upfront payment of approximately $295 million for the 73 percent stake not yet owned, up to $92 million upon achievement of certain clinical and regulatory milestones as well as additional revenue-based payments for the next three years.+

"The more than $6 billion electrophysiology market continues to expand, growing double digits year-over-year, and adding this technology to our existing portfolio enables Boston Scientific to be the only company to offer physicians comprehensive therapeutic options they can select based on clinical preference and individualized patient needs," said Scott Olson, senior vice president and president, Rhythm Management, Boston Scientific.

Farapulse became the first company to commercialize a cardiac PFA technology after receiving CE Mark for the FARAPULSE PFA System in Europe in the first quarter of 2021. The company also initiated its pivotal IDE trial in the U.S. – the ADVENT trial – in March 2021. All trial sites have been identified and more than 100 patients have been enrolled to date in the prospective, randomized trial. The study is comparing the FARAPULSE PFA System to standard-of-care ablation in patients with paroxysmal – or intermittent – AF with a primary endpoint of freedom from AF at 12 months after a single ablation procedure.

"We are encouraged by the positive reception to the commercial launch of the FARAPULSE PFA System in Europe, which we believe underscores the demand for a simpler way to treat AF," said Allan Zingeler, president and chief executive officer, Farapulse, Inc. "The strength and breadth of the Boston Scientific team will position this breakthrough technology for success and accelerate progress towards regulatory approval in the U.S."

On an adjusted basis, the transaction is expected to be slightly dilutive to adjusted earnings per share (EPS) in 2021 and 2022, which Boston Scientific expects to offset via internal cost efficiencies and trade-offs. On a GAAP basis, the transaction is expected to be more dilutive due to amortization expense and acquisition-related charges, except for a one-time gain to be recognized at closing associated with our previously held equity interest in Farapulse. The transaction is anticipated to close in the third quarter of 2021, subject to customary closing conditions.

*In the U.S., the Farapulse platform is an investigational device and not available for sale.

+Preceding consideration of current equity ownership, debt and other closing adjustments, the transaction price consists of $450 million up front, up to $125 million upon achievement of certain clinical and regulatory milestones as well as additional revenue-based payments through calendar year 2023.