Antibodies derived from mouse or human sources use the surface formed by complementarity determining regions (CDRs) on the variable regions of the heavy chain/light chain heterodimer, which typically forms a relatively flat binding surface. Alternative species, particularly camelids and bovines, provide a paradigm for antigen recognition through novel domains which form the antigen binding site. However, for camelids, heavy chain antibodies bind antigen with only a single heavy chain variable region, in the absence of light chains. Meanwhile, in bovines, ultralong CDR-H3 regions form an independently folding mini-domain, which protrudes far out from the surface of the antibody and forms a “stalk and knob” structure which is diverse in both its sequence and disulfide patterns. The “knob” (Picobody) component can be expressed as an independent antigen binding domain. At ~4-6 kDa, these are three times smaller than a camelid “nanobody”, and are the smallest known antibody fragment. These atypical antigen binding sites of bovines potentially provide the ability to interact with different antigenic determinants, particularly recessed or concave surfaces, compared to traditional antibodies.
Sources: Company Website. Company Presentation.
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As mentioned above, HILS needs your full focus now based on several potential catalysts. Check them out:
No. 1 HILS Potential Catalyst - A Low Float Could Lead To Explosive Volatility (Again!)
According to the Yahoo Finance website, HILS has a low float.
The website reports this profile to have roughly 11.46Mn shares in its float.
Why is that important? It's important on one crucial level. Volatility.
Could more positive 2023 company news help provide a near term spark?
Remember: This was an explosive breakout idea previously that ran approximately 100+% in the short term after I brought it to your attention earlier this year.
A low float may have created the potential for such a volatile move...
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No. 2 HILS Potential Catalyst - Company Enters Agreement To Acquire Key Asset (Itching May Be Meeting Its Match)
Hillstream Enters into an Exclusive Option Agreement to Acquire a Clinical Stage Asset for Chronic Pruritis
Anticipate completion of Phase 1 & Phase 2 clinical trials in chronic pruritis over the next approximately 12 months
Seeking first approval in an orphan disease, PBC, for the treatment of moderate to severe chronic pruritis in which more than 70% of patients suffer from chronic pruritis
BRIDGEWATER, N.J., Sept. 11, 2023 (GLOBE NEWSWIRE) -- Hillstream BioPharma, Inc. (Nasdaq: HILS) ("Hillstream" or the "Company"), a biotechnology company developing therapeutic candidates targeting drug resistant and devastating cancer announces an exclusive option agreement to acquire a clinical stage asset, AV104, with a recently approved IND. AV104 has a dual mechanism of action by affecting multiple receptors, known to suppress chronic, debilitating pruritis or “uncontrollable itching.” The Company intends to first seek approval in an orphan disease for the treatment of moderate to severe cholestatic pruritis in patients with primary biliary cholangitis (PBC), a rare form of liver disease with no known cure in which more than 70% of patients suffer from chronic pruritis.
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Hillstream believes AV104 has expansion opp's in treating chronic pruritogenic conditions associated with cholestatic liver disease as well as other liver related and as non-liver related diseases including fatty and alcoholic liver diseases, non-alcoholic liver diseases and certain types of hepatitis. Chronic pruritis is significant in liver diseases as well as chronic kidney diseases, hemodialysis and atopic dermatitis.
“The past year has been a period of transformational change for our company,” said Randy Milby, CEO of Hillstream. “This exclusive option allows the company to bring a clinical-stage asset into the organization as we shift into a patient-focused biotechnology organization. This signifies our next step as we grow into a business model focused on clinical development.”
Read the full article here.
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No. 3 HILS Potential Catalyst - HillStream Expands Collaboration And License Agreement To Advance Game-Changing "Knob" Biologics
Hillstream Advances Next-Gen Multispecific Antibodies for Solid Tumors with Lead HER2/HER3 Program, HSB-3215
Collaboration adds multiple modular swappable antigen recognition regions to lead program, HSB-3215, a bispecific antibody targeting novel epitopes on HER2/HER3 receptors
Capitalizes on “Knob” biologics (PicobodiesTM) for tumor targeting, extends partnership to include validated target, HER3
IND filing for HSB-3215 planned in 2024
BRIDGEWATER, N.J., July 20, 2023 (GLOBE NEWSWIRE) -- Hillstream BioPharma, Inc. (“Hillstream”, the “Company”) today announced the expansion of its collaboration with Minotaur Therapeutics, Inc. (“Minotaur”) and its license agreement with OmniAb, Inc. (“OmniAb”) to advance the development of next generation targeted Knob biologics (PicobodiesTM) against HER3 and a new undisclosed oncology target. Hillstream will collaborate with Minotaur using OmniAb’s “OmniTaur™” technology to discover targeted biotherapeutic Picobodies complimenting Hillstream’s most advanced program, HSB-3215, a HER2/HER3 bispecific antibody (BsAb).
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Dr. Vaughn Smider, Founder and Chief Executive Officer of Minotaur, stated “We are excited to continue Minotaur’s collaboration with Hillstream to progress novel next-generation targeted cancer biologics.”
Randy Milby, Chief Executive Officer of Hillstream, stated, “We are extremely pleased with the progress made to date. The Knob biologics program continues to be a great addition to our portfolio as we rapidly progress our lead asset HSB-3215 towards an IND. Hillstream is now poised to develop a novel technology for creating multiple proteins to enhance targeted cancer immunotherapy.”
Read the full article here.
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No. 4 HILS Potential Catalyst - A Pipeline Reprioritization Aims To Provide Near-Term Value Creation
Hillstream BioPharma Announces Strategic Reprioritization of Pipeline to Targeting HER2/HER3 Solid Tumors via Bispecific and ADC Antibodies and Biologics
Lead bispecific antibody, HSB-3215 designed to target novel conformational epitopes on high value validated targets, HER2 and HER3
Focus on optimizing ADCs to generate a more potent Bystander Effect and proprietary novel bovine-derived biologic platform, PicoKnobTM, targeting undruggable epitopes on PD-1 and TROP2
Experienced biopharmaceutical executive joins as Chief Operating Officer to spearhead execution of ADC and biologic strategy
BRIDGEWATER, N.J., July 10, 2023 (GLOBE NEWSWIRE) -- Hillstream BioPharma (Nasdaq: HILS) a biotechnology company developing innovative therapeutic candidates targeting drug resistant and devastating cancers that can make a difference in patients’ lives, today announced a strategic reprioritization of its pipeline and provided a corporate update. The strategic assessment took into account, the pipeline’s near-term value creation opp. and other factors. Hillstream will focus its pipeline on advancing novel oncology assets with the greatest potential and strong competitive profiles to address unmet needs across multiple solid tumors, such as bispecific antibodies and ADCs targeting novel conformational epitopes on high value validated targets, HER2 and HER3, with a more potent Bystander Effect.
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Hillstream’s lead asset, HSB-3215 is designed as a bispecific humanized immunoglobulin containing two arms targeting the extracellular domains of HER2 and HER3. HSB-3215 binds to both overlapping and different epitopes on HER2 when compared to trastuzumab, the first approved antibody against HER2, while adhering to novel epitopes on HER3, thus creating novel conformational epitopes. The Company intends to develop this novel BsAb and file an IND application with the US FDA late next year.
By exploiting the “Bystander Effect”, a key aspect of ADCs which has been recently highlighted by the improved clinical efficacy of Daiichi Sankyo/AstraZeneca’s ENHERTU® (trastuzumab deruxtecan), the Company plans to optimize its BsAb pipeline with BiSpecific ADCs, i.e. BiSpecific antibodies conjugated with novel toxin payloads which are optimized to generate a more powerful Bystander Effect. ADCs are comprised of a targeting antibody chemically conjugated via a proprietary linker to a powerful, cancer-killing compound/toxin (payload). With a BsAb backbone utilizing HSB-3215, the Company intends to develop novel ADCs, targeting HER2/HER3 and better direct a payload to cancer cells overexpressing these receptors, while healthy cells don’t take up the unwanted compound.
Hillstream also intends to further enhance its previously announced collaborations with Applied Biomedical Science Institute (ABSI) and Minotaur to develop novel bovine-derived biologics in multiple formats against highly validated targets, including PD-1, HER2 and TROP-2, referred to as PicoKnobsTM. An update regarding these collaborations will be announced during an R&D Day in the third quarter.
“Our recently announced collaborations with ABSI are transforming Hillstream into a focused and targeted cancer biologics company,” said Randy Milby, Chairman and CEO of Hillstream. “With the HER2 and HER3 platform, we are building a diverse foundation of targeted biologics which can be utilized for our current portfolio as well for future in-licensed assets. We are confident that our focused approach and experienced management team best positions us for success.”
The Company also announced the appointment of Sireesh Appajosyula, Pharm. D .as as Chief Operating Officer (COO). Sireesh brings over 20 years of experience in creating and advising biotechnology companies such as 9 Meters Biopharma Inc. through targeted transactions thus creating a pipeline as well as accessing the public capital markets. He was responsible for corporate development including portfolio strategy, in-licensing transactions and alliances for 9 Meters’s core assets as well as monetization of non-core assets. Previously, he spent eight years at Salix Pharmaceuticals, Inc. in various roles including medical & clinical affairs, product commercialization and business development culminating in Salix’s acquisition for $16Bn by Bausch Health. Prior to Salix, Sireesh held increasing roles and responsibilities at Amgen, Chiesi (Critical Therapeutics) and Sanofi S.A. (Aventis). Sireesh holds a Doctor of Pharmacy degree from the Ernest Mario College of Pharmacy at Rutgers University in New Jersey.
“I am thrilled to join Hillstream and look forward to working alongside the team as we further our development programs. I believe the Company’s precision oncology strategy with the current HER2/HER3 antibody programs and pipeline have the potential to bring much needed treatments to cancer patients,” said Dr. Appajosyula.
Read the full article here.
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No. 5 HILS Potential Catalyst - Exclusive Agreement With Leading Institute Will Help Build Antibody Platform To Advance Pipeline
Hillstream BioPharma Licenses Technology to Develop Proprietary HER2 and HER3 Antibody Drug Conjugates against Drug-Resistant Breast, Lung, Gastric, and Ovarian Cancers
Anti-HER2 and Anti-HER3 monoclonal antibodies designed to have a high drug-to-antibody ratio intended enhance the bystander killing effect and be effective against a number of epithelial tumors
Antibody CDRs against HER2 and HER3 Conformational Domain Bridging Epitopes can be used in multiple formats including bi- and tri-specific antibodies, antibody drug conjugates (ADCs), CAR-T and CAR-NKs
BRIDGEWATER, N.J., July 06, 2023 (GLOBE NEWSWIRE) -- Hillstream BioPharma, Inc. (Nasdaq: HILS) ("Hillstream" or the "Company"), a biotechnology company developing therapeutic candidates targeting drug resistant and devastating cancers using immuno-oncology targeted novel biologics, today announced the signing of an exclusive agreement with Applied Biomedical Science Institute (ABSI) to license technology for human antibodies targeting novel HER2 and HER3 Conformational Epitopes. The goal is to develop proprietary multi-format biologics, including bi-specific antibodies, and antibody drug conjugates (ADCs). The HER2/HER3 binding ADC is targeted to have a high drug-to-antibody ratio which should increase the anti-tumoral efficacy with an enhanced bystander killing effect. Hillstream intends to combat drug resistant cancers such as HER2-positive metastatic breast cancer, gastric cancer, lung cancer and ovarian cancer.
The ErbB family of cell surface proteins, including ErbB2 or HER2 (human epidermal growth factor receptor) and Erb3 or HER3, are some of the most well-known and validated oncology drug targets. Antibodies and biologics against HER2 starting with HERCEPTIN® (trastuzumab) approved in 1998 for breast cancer, and PERJETA®, KADCYLA® and PHESGO® generated $8.4Bn in 2022 sales for Roche/Genentech. These antibodies bind to domains II or IV of the extracellular portion of the HER2. HER2 is also one of the most validated antigens for antibody drug conjugates (ADCs) to treat HER2 positive cancers with two approved antibodies, Roche/Genentech’s KADCYLA® and Daiichi Sankyo/AstraZeneca’s ENHERTU®.
The Applied Biomedical Science Institute has developed technology to target novel functional epitopes of the cancer targets HER2 and HER3. The monoclonal antibodies being developed at ABSI are distinct from the currently approved anti-HER2 antibodies. ABSI has granted Hillstream an exclusive license agreement, and Hillstream will have the opportunity to develop HER2 and HER3 antibodies, including multi-specific, ADC, and Quatramer-based therapeutics utilizing portions of these antibodies.
“We look forward to this opp. to work with Dr. Smider and the Applied Biomedical Science Institute,” said Randy Milby, CEO of Hillstream. “This agreement allows us to build our antibody platform to advance our immune-oncology biologic pipeline with HER2 and HER3 with bi-specifics and ADC agents targeting highly aggressive drug-resistant metastatic tumors, which represents a major unmet need for patients.”
Read the full article here.
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HILS Recap - The Top Potential Breakout Catalysts To Know Right Now
No. 1 - A Low Float Could Lead To Explosive Volatility (Again!)
No. 2 - Company Enters Agreement To Acquire Key Asset (Itching May Be Meeting Its Match)
No. 3 - HillStream Expands Collaboration And License Agreement To Advance Game-Changing "Knob" Biologics
No. 4 - A Pipeline Reprioritization Aims To Provide Near-Term Value Creation
No. 5 - Exclusive Agreement With Leading Institute Will Help Build Antibody Platform To Advance Pipeline
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Coverage is reinitiated on HILS. When you have a chance, do this:
