A trio of leads for a hopeful future

Collaboration between Compugen and BioLineRx begins with three peptides but could lead to much more

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JERUSALEM—Biopharmaceutical development company BioLineRxLtd. has entered into a collaboration agreement with fellow Israeli companyCompugen Ltd. for early- to mid-stage development of mutually selected drugcandidates for the treatment of various diseases, ranging from acute andchronic inflammatory diseases to cardiac diseases, retinopathy and cancer.
Under the deal, Tel Aviv-based Compugen is providingpromising drug candidates that were identified using its predictive in-silico drug discovery platforms. Forits part, BioLineRx is to develop these candidates through Phase II clinicaltrials, with an eye toward eventually licensing them to pharmaceuticalcompanies for advanced clinical development and commercialization.
The collaboration is getting its start with the selection ofthree Compugen-discovered peptides. Two of the peptides, named CGEN-855 andCGEN-856, will enter BioLineRx's main product pipeline as BL-7070 and willfocus on preventing and treating cardiovascular diseases by controllinginflammation and reducing hypertension. The third peptide, CGEN-25017, willenter BioLineRx's pipeline as BL-8010 and is intended for the treatment ofdiseases characterized by excessive growth of new blood vessels, such asretinopathy and cancer. All three have already undergone proof-of-conceptanimal studies.
Both parties will continue to evaluate otherCompugen-discovered drug candidates for development by BioLineRx.
"Part of the collaborative framework agreement is to puttogether a committee made up of people from both companies—on the business endand on the science side—because there is a real interest on both sides tointeract more proactively," Josh Hexter, BioLineRx's executive director ofcorporate in-licensing, tells ddn,adding that in years past, BioLineRx had explored possible one-off projectswith Compugen that never took off. "When we did due diligence for this morestrategic and long-term kind of collaboration, we looked through what they hadin their discovery pipeline and flushed through it to find some promisingpeptides, but we're also interested in sitting down with them to outlinetargets and indications of interest to us and put those through their platformto maybe get some other interesting assets."
"Joining forces with the proven drug validation anddevelopment skills of BioLineRx to advance the development of such previouslydiscovered promising Compugen peptide discoveries served as a natural fit forboth companies," Tsipi Keren-Lehrer, Compugen's director of businessdevelopment, tells ddn. "This is alsothe reason why the parties will continue to evaluate other Compugen-discovereddrug candidates for development by BioLineRx. The business model of our companyis to maximize the number of Compugen's product candidates in the pipelines ofpharma and biotech companies under milestones, royalties and otherrevenue-sharing arrangements. We therefore constantly look for excellentpartners in order to advance the development and commercialization of ourassets."
The partnership is made all the more perfect and promising,Hexter notes, by the fact that "Compugen is great at discovery but doesn't havemuch of a development arm, whereas we're good at development but don't reallyhave a discovery arm. We see this deal as highly strategic and co-developmentin nature; we won't just sit on our hands and wait for another list ofpeptides, but rather see how we can best use Compugen's platform to find newleads to take forward."
In the news release about the deal, BioLineRx CEO Dr.Kinneret Savitsky said much the same, noting, "This mutually beneficialagreement is in keeping with our company strategy of seeking promisingtherapeutic candidates for our product pipeline and developing them throughPhase II clinical trials."
Compugen's president and CEO, Dr. Anat Cohen-Dayag, addedthat as part of his company's process of establishing its broadly applicablepredictive discovery capabilities, "a number of promising potential therapeuticpeptides and other potential drug candidates were discovered that are not inthese main areas of focus. The goal of this collaboration with BioLineRx andothers which have been, or will be, announced, is to advance certain of thesepromising discoveries, without the need for further Compugen financialresources, but with Compugen sharing in the value created."
CGEN-855 is a novel peptide agonist of the FPRL1 G-proteincoupled receptor (GPCR), discovered by Compugen's GPCR Peptide Ligand DiscoveryPlatform. FPRL1 is expressed by various immune system cells, and its activationpromotes resolution of inflammation, leading to pronounced anti-inflammatoryactivity. Accordingly, CGEN-855 has shown anti-inflammatory activity whentested in animal models of acute inflammation and has exhibited acardioprotective effect in models of acute myocardial infarction in mice andrats. CGEN-855 was also shown to be beneficial in an animal model ofinflammatory bowel disease. These results support the therapeutic potential ofCGEN-855 in treating acute and chronic inflammation, as well as cardiovasculardiseases.
CGEN-856 is a novel ligand of the MAS GPCR receptor, one ofthe key components of the renin-angiotensin system which controls bloodpressure and water balance in the body. This peptide was discovered byCompugen's GPCR Peptide Ligand Discovery Platform. CGEN-856 induced relaxationof rat and murine aortas, reduced in-vivocardiac remodeling induced by isoproterenol or ischemia and displayedanti-hypertensive effects as well as cardiac and renal anti-fibrotic effects.CGEN-856 may thus be a useful therapeutic agent in conditions such ashypertension, heart failure, cardiac remodeling, myocardial infarction, renalfibrosis and other cardiovascular pathologies.
CGEN-25017 is a novel peptide antagonist of theAngiopoietin/Tie-2 pathway that is crucial for angiogenesis, blood vesselmaturation and vascular endothelium integrity. The peptide has shown positivetherapeutic effects in an animal model of retinopathy. CGEN-25017, which wasinitially discovered using Compugen's Disease-Associated Conformation BlockersDiscovery Platform, had previously demonstrated significant inhibitory activityin an animal model of retinopathy and in two other models of angiogenesis.Based on its anti-angiogenic properties, CGEN-25017 has potential therapeuticutility for additional diseases involving pathological angiogenesis such ascancer and inflammatory conditions, including psoriasis and rheumatoidarthritis.

Compugen in $8million research deal with Baize Investments
TEL AVIV, Israel—Compugen Ltd. also recently announced an $8million research funding agreement with Baize Investments Ltd., a privatecorporation also based in Israel that invests in innovative medicaltechnologies.
The funding agreement follows an earlier pact between thetwo parties formed in December 2010, in which Compugen received $5 million insupport of the initiation of its monoclonal antibody (mAb) pipeline program.
Baize will receive a financial interest in therapeutic mAbproduct candidates to be developed against 12 specified Compugen-discoveredtargets in the field of oncology, provided that any such mAb product candidateseither achieves a successful animal disease model during the next three years,and/or is licensed out to third parties for final development andcommercialization. Baize is entitled to a percentage of future paymentsreceived by Compugen from third parties from any out-licensing for furtherdevelopment and/or commercialization. In addition, Baize has the right, duringthe first quarter of 2014, to waive its rights to receive all such futurepayments in exchange for 1.45 million Compugen ordinary shares.
Of Compugen's pipeline, Murray Goldman, Baize's chairman,stated, "This is anticipated to lead to significant new therapeutic candidatesaddressing key unmet needs in cancer treatment, which could meaningfullycontribute to the well-being of humanity." 

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