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The first patient has been dosed in a phase I/IIa fluorescence-guided surgical clinical trial evaluating pHLIP^® ICG imaging agent. The purpose of this study is to see whether the use of the fluorescent imaging agent pHLIP^® ICG and NIRF imaging during surgery is a safe approach that may allow the surgeon to image tumor bed and established tumor margins. The ClinicalTrials.gov identifier is NCT05130801, https://clinicaltrials.gov/ct2/show/NCT05130801

The U.S. Food and Drug Administration (FDA) has provided green light to initiate first in human clinical studies of pHLIP^® ICG imaging agent.  pHLIP^® ICG will be administered to breast cancer patients in a phase 1/2a fluorescence-guided surgical trial at Memorial Sloan Kettering Cancer Center. Fluorescence guidance by pHLIP^® ICG during surgical procedures is expected to improve visualization of primary tumor masses and satellite cancerous lesions and allow accurate margin delineation to improve surgical outcomes.

Cybrexa Therapeutics announced that the first patient has been dosed in a Phase 1/2 clinical trial evaluating CBX-12 (alphalex™-exatecan), the company’s lead therapeutic candidate. CBX-12 or alphalex™-exatecan is a pHLIP® Exatecan peptide conjugate: http://cybrexa.com/news/#

About Cybrexa: Cybrexa is a privately-held biotechnology company dedicated to developing next-generation tumor-targeted cancer therapies using its alphalex™ platform. The Company’s lead candidate, CBX-12, an alphalex™-exatecan conjugate, is expected to enter Phase I/II in 2021 in advanced solid tumors. Cybrexa also has other preclinical toxin conjugate programs as well as synthetic lethality programs. Cybrexa was founded by physician-scientists and has an experienced management team that has built numerous successful life sciences companies. For more information about Cybrexa, please visit www.cybrexa.com.

Media Contact: media@cybrexa.com

Investor Relations
Westwicke, an ICR Company Stephanie Carrington
Stephanie.carrington@icrinc.com
646-277-1282

The Memorial Sloan Kettering Cancer Center and the University of Rhode Island granted pHLIP, Inc exclusive worldwide commercial rights for the composition of matter and methods of use of pHLIP® compounds protected by a patent application developed by founders of the company and filed in September 22, 2020.

The University of Rhode Island and Yale University granted pHLIP, Inc exclusive worldwide commercial rights for methods of use of pHLIP® compounds protected by a patent application developed by founders of the company and filed in May 2020.

Pharmacology and toxicology studies with the pHLIP® ICG imaging agent for fluorescence-guided surgery were completed at Charles River. No adverse effects were seen at doses of 30x the proposed starting human dose either after a single IV dose or after daily IV injections into dogs for 7 days. Also, a cardiovascular telemetry study was performed on dogs, a pharmacological safety assessment and micronucleus test were performed on the central nervous system of Sprague Dawley rats, and local tolerance and irritancy tests were carried out on rabbits. No adverse effects were observed.

pHLIP, Inc and CordenPharma entered into a Master Development and Supply Agreement for GMP manufacturing of a variety of pHLIP^® Drug Conjugate APIs.

About pHLIP, Inc: pHLIP, Inc is a privately-held clinical-stage biopharmaceutical company dedicated to improving patient outcomes and saving lives by using our peptide-based targeted delivery platform to treat cancer, inflammation and other acidic tissue diseases. Our proprietary pHLIP® (pH-Low Insertion Peptide) technology targets metabolically active acidic cells in diseased tissues. Therapeutic and imaging molecules are anchored to the surfaces of acidic diseased cells or translocated and released directly into acidic diseased cells by pHLIP® peptides. Our business strategy is to commercialize pHLIP® technology by developing pHLIP® Drug Conjugates (PDCs) from our own pipeline or by partnering with other biopharmaceutical companies to enable or enhance the safety and efficacy of their imaging agents, drugs or drug candidates. The composition of matter and methods of use of our pH peptides are protected by issued and pending patents, which have been exclusively licensed from Yale, the University of Rhode Island and the Memorial Sloan Kettering Cancer Center. For more information visit: www.phlipinc.com

About CordenPharma: CordenPharma, the global pharmaceutical manufacturing platform of ICIG, is a full-service Contract Development & Manufacturing Organization for APIs, Drug Products, and Packaging. Through cGMP facilities across Europe and the US organized under four Technology Platforms – Peptides, Lipids & Carbohydrates, Injectables, Highly Potent & Oncology, and Small Molecules – CordenPharma experts translate complex projects at any stage of development into high-value products.

pHLIP, Inc and Cybrexa Therapeutics entered into Sub-licensing Agreements in December 2019. pHLIP, Inc granted Cybrexa Therapeutics exclusive worldwide development and commercialization rights to use pHLIP® peptides in the development of oncology therapeutics that include DNA damage repair inhibitors and cytotoxic molecules.

About pHLIP, Inc: pHLIP, Inc is a privately-held clinical-stage biopharmaceutical company dedicated to improving patient outcomes and saving lives by using our peptide-based targeted delivery platform to treat cancer, inflammation and other acidic tissue diseases. Our proprietary pHLIP® (pH-Low Insertion Peptide) technology targets metabolically active acidic cells in diseased tissues. Therapeutic and imaging molecules are anchored to the surfaces of acidic diseased cells or translocated and released directly into acidic diseased cells by pHLIP® peptides. Our business strategy is to commercialize pHLIP® technology by developing pHLIP® Drug Conjugates (PDCs) from our own pipeline or by partnering with other biopharmaceutical companies to enable or enhance the safety and efficacy of their imaging agents, drugs or drug candidates. The composition of matter and methods of use of our pH peptides are protected by issued and pending patents, which have been exclusively licensed from Yale, the University of Rhode Island and the Memorial Sloan Kettering Cancer Center. For more information visit: www.phlipinc.com

About Cybrexa: Cybrexa is a privately-held biotechnology company dedicated to developing next-generation tumor-targeted cancer therapies using its alphalex™ platform. The Company’s lead candidate, CBX-12, an alphalex™-exatecan conjugate, is expected to enter Phase I/II in 2021 in advanced solid tumors. Cybrexa also has other preclinical toxin conjugate programs as well as synthetic lethality programs. Cybrexa was founded by physician-scientists and has an experienced management team that has built numerous successful life sciences companies. For more information about Cybrexa, please visit www.cybrexa.com.

Media Contact: media@cybrexa.com

Investor Relations
Westwicke, an ICR Company Stephanie Carrington
Stephanie.carrington@icrinc.com
646-277-1282

A proof of concept human 18F PET nuclear imaging clinical study with pHLIP® peptide is initiated at the Memorial Sloan Kettering Cancer Center. The ClinicalTrials.gov Identifier is NCT04054986.

Pharmacology and toxicology studies with the pHLIP® ICG imaging agent for fluorescence-guided surgery were completed at MSKCC. No adverse effects were observed in mice at doses of 25x the proposed starting human dose, either after a single IV dose or after daily dosing for 7 days.

pHLIP, Inc and Iris Biotech, GmbH entered into a Master Development and Supply Agreement for non-GMP synthesis of pHLIP® Drug Conjugates

About pHLIP, Inc: pHLIP, Inc is a privately-held clinical-stage biopharmaceutical company dedicated to improving patient outcomes and saving lives by using our peptide-based targeted delivery platform to treat cancer, inflammation and other acidic tissue diseases. Our proprietary pHLIP® (pH-Low Insertion Peptide) technology targets metabolically active acidic cells in diseased tissues. Therapeutic and imaging molecules are anchored to the surfaces of acidic diseased cells or translocated and released directly into acidic diseased cells by pHLIP® peptides. Our business strategy is to commercialize pHLIP® technology by developing pHLIP® Drug Conjugates (PDCs) from our own pipeline or by partnering with other biopharmaceutical companies to enable or enhance the safety and efficacy of their imaging agents, drugs or drug candidates. The composition of matter and methods of use of our pH peptides are protected by issued and pending patents, which have been exclusively licensed from Yale, the University of Rhode Island and the Memorial Sloan Kettering Cancer Center. For more information visit: www.phlipinc.com

About Iris Biotech, GmbH: Having a holistic view of the world of peptide chemistry, Iris Biotech GmbH today is the number one address for any unusual compounds required for the synthesis and modification of peptides. Our mission as qualified supplier is to support our customers in their ongoing projects from research scale to commercial production by providing the most novel substances and latest technologies together with comprehensive analytics and documentation. Recent developments in combination therapy, antibody-drug conjugation, and related advanced concepts like pHLIP® Drug Conjugates (PDCs) are based on linking together two compounds with different functionalities. Historically, linker moieties used to represent simple conjugation elements, but have since developed into crucial parts of all the various kinds of drug conjugates nowadays on the market. Chain length and physicochemical properties, as well as triggered traceless release properties have become important parameters for linker molecules that significantly influence the pharmacological characteristics and efficacy of the main actors in the drug assembly. The ever-growing sophistication and variation in linker design have given rise to a new and distinct field of knowledge in synthetic chemistry termed Linkerology. Keeping step with the latest advances in this field, Iris Biotech has developed a panoply of over 100 specialized and cutting-edge linker constructs, adding to our existing portfolio of some 1000 conventional aliphatic and PEG-based linkers. For more information visit: https://www.iris-biotech.de

Peter Glazer, Robert E. Hunter Professor of Therapeutic Radiology and Professor of Genetics, Chair of Therapeutic Radiobiology Department, Yale Medical School ( https://medicine.yale.edu/profile/peter_glazer/ ) joined the pHLIP, Inc Scientific Advisory Board. Peter has studied the pHLIP® technology for many years and brings expertise in cancer biology, genetics, therapeutics and radiation oncology.

The University of Rhode Island and Yale University granted pHLIP, Inc an exclusive worldwide commercial rights for the composition of matter and methods of use of pHLIP® compounds protected by a patent application developed by founders of the company and filed in in April, 2019.

An IND package was filed with the FDA by MSKCC to initiate a proof of concept 18F PET nuclear imaging clinical study with pHLIP® peptide.

Ruslan Medzhitov, Sterling Professor of Immunobiology, Yale Medical School, and an Investigator of the Howard Hughes Medical Institute, (https://medicine.yale.edu/immuno/people/ruslan_medzhitov.profile) joined the pHLIP, Inc Scientific Advisory Board. Ruslan brings expertise in inflammation, immunology and immuno-oncology

The University of Rhode Island and Yale University granted pHLIP, Inc exclusive worldwide commercial rights for the composition of matter and methods of use of pHLIP® compounds protected by four patent applications developed by founders of the company and filed in January 2019.

Mark Lemmon, David A. Sackler Professor of Pharmacology and co-director of the Cancer Biology Institute, Yale Medical School (https://medicine.yale.edu/pharm/people/mark_lemmon.profile) joined Scientific Advisory Board. Mark brings expertise in cell and cancer biology, pharmacology and kinase inhibitors.

The Memorial Sloan Kettering Cancer Center and the University of Rhode Island granted pHLIP, Inc exclusive worldwide commercial rights for the composition of matter and methods of use of pHLIP® compounds protected by a patent application developed by founders of the company and filed in July 2016.

After comprehensive preclinical studies and the demonstration of pHLIP® targeting of a variety of solid tumors and cancerous lesions in human tissues, pHLIP, Inc named its first candidate, pHLIP® ICG. pHLIP® ICG is a targeted version of ICG, a widely used fluorescence imaging probe. pHLIP^® anchors ICG to tumor cells, serving as a surgical imaging agent for the visualization and precise removal of a broad spectrum of tumors to improve surgical outcomes. pHLIP^® ICG can also image blood flow in a variety of surgical procedures.

The Company raised about $4M in a second part of private financing to fund product development and the IP portfolioThe Company raised about $4M in a second part of private financing to fund product development and the IP portfolio

pHLIP, Inc and Charles River entered into a Master Service Agreement for non-GLP and GLP animal efficacy and toxicology studies of a variety of pHLIP® Drug Conjugates.

About pHLIP, Inc: pHLIP, Inc is a privately-held clinical-stage biopharmaceutical company dedicated to improving patient outcomes and saving lives by using our peptide-based targeted delivery platform to treat cancer, inflammation and other acidic tissue diseases. Our proprietary pHLIP® (pH-Low Insertion Peptide) technology targets metabolically active acidic cells in diseased tissues. Therapeutic and imaging molecules are anchored to the surfaces of acidic diseased cells or translocated and released directly into acidic diseased cells by pHLIP® peptides. Our business strategy is to commercialize pHLIP® technology by developing pHLIP® Drug Conjugates (PDCs) from our own pipeline or by partnering with other biopharmaceutical companies to enable or enhance the safety and efficacy of their imaging agents, drugs or drug candidates. The composition of matter and methods of use of our pH peptides are protected by issued and pending patents, which have been exclusively licensed from Yale, the University of Rhode Island and the Memorial Sloan Kettering Cancer Center. For more information visit: www.phlipinc.com

About Charles River: Charles River provides essential products and services to help pharmaceutical and biotechnology companies, government agencies and leading academic institutions around the globe accelerate their research and drug development efforts. Our dedicated employees are focused on providing clients with exactly what they need to improve and expedite the discovery, early-stage development and safe manufacture of new therapies for the patients who need them.

The University of Rhode Island and Yale University granted pHLIP, Inc exclusive worldwide commercial rights for the composition of matter and methods of use of pHLIP® of compounds protected by a patent application developed by founders of the company and filed in June 2017.

The Company raised about $2M in private financing to fund product development and the IP portfolio

Published in UroToday

In modern medicine, we increasingly find ourselves at the interface of technological advances and scientific breakthroughs.  As techniques and instrumentation become ever more precise, research into specific disease processes progressively focuses on unique microscopic and molecular features that might lend themselves as therapeutic target.  Interestingly the mechanisms behind the molecules at work in the study at hand rely on basic cancer biology principles, namely that of tumor acidity and disease microenvironment.

In the present study our group showed the utility of intravesical instillation of the ICG pHLIP^® (ICG is a FDA approved near infrared fluorescent dye and pHLIP^® is a pH (Low) Insertion Peptide, which targets tumor acidity) construct for bladder tumor identification and staging.  The molecule was also able to identify dysplastic tissue which may represent a premalignant lesion.  If premalignant lesions could be identified in a reliable and actionable fashion this might offer the opportunity of preventing disease progression and subsequent patient morbidity.  Furthermore, in an era of rising healthcare costs for both patients and institutions, early detection and prevention may represent significant savings in treatment and follow up surveillance costs.

There are many potential novel applications for this molecule moving forward.  As described in the manuscript, our utilization of ICG as the molecule bound to pHLIP^® is in many ways a proof of principle.  Having demonstrated the preferential avidity of pHLIP for bladder cancer cells over normal tissue, it is our intent to utilize the pHLIP^® molecule to deliver alternative agents such as chemotherapeutics in future experiments.  Additionally, our collaborators have demonstrated the feasibility of using pHLIP^® in PET imaging for accurate tumor identification and characterization¹. While the current study was performed on ex-vivo specimens, preliminary data on toxicity of the molecule are encouraging and a natural next step will be immediate preoperative intravesical instillation for patients undergoing transurethral bladder tumor resections to aid in tumor identification and perhaps even allow for real time tumor staging.

As a pilot study, our publication requires further validation and investigation in a larger population of patients.  Further efforts will focus on the prospects for intravenous administration of this or similar constructs for targeted fluorescence, contrast or drug delivery. Current foci for investigation at our institution include IRB approved projects applying the ICG pHLIP^® construct to upper tract urothelial and renal cell neoplasms for tumor identification and staging purposes.  Preliminary results are encouraging as we optimize specimen preparation regimens.

With the dubious honor of having the highest per capita incidence of bladder cancer in the nation, Rhode Island represents a unique patient population.  We thank the patients who participated in this study and those who will assist in studies to come.  With the application of this and other burgeoning technologies, we hope to improve the quality of care delivered to bladder cancer patients both locally and abroad.

The University of Rhode Island and Yale University granted pHLIP, Inc exclusive worldwide commercial rights for the composition of matter and methods of use of pHLIP® compounds protected by a patent application developed by founders of the company and filed in September 2016.

Inventors of the pHLIP® technology and founders of the Company from Yale University and the University of Rhode Island received a competitive renewal of their NIH grant for 4 years (2016-2020) for the investigation and development of new pHLIP® Drug Conjugates (PDCs).

The University of Rhode Island granted pHLIP, Inc exclusive worldwide commercial rights for the composition of matter and methods of use of cyclic pH-compounds protected by patent applications developed by the founders of the company and filed in March of 2016.

The University of Rhode Island and Yale University granted pHLIP, Inc exclusive worldwide commercial rights for the composition of matter and methods of use of pHLIP® compounds developed by founders of the company and protected by a comprehensive portfolio of patent applications.