Valo Health Announces Publication of the Journal of Clinical Investigation of a New Therapeutic Approach to Improve CD8+ T Cell Function

Novel engineered cytokine triggers a unique signaling pathway in preclinical studies

Boston, MA (June 2, 2022) Valo Health, Inc (“Valo”), the tech­nol­o­gy com­pa­ny focused on trans­form­ing the drug dis­cov­ery and devel­op­ment process using human-cen­tric data and arti­fi­cial intel­li­gence, announced a proof of con­cept for using its pre­clin­i­cal asset, OPL-0101, to tar­get CD8+ T cells, in the cur­rent issue and fea­tured on the cov­er of the Jour­nal of Clin­i­cal Inves­ti­ga­tion Insight (JCI).

The data pre­sent­ed in JCI demon­strates that OPL-0101 (referred to as OMCPmutIL‑2 in the paper) trig­gers improved CD8+ T cell func­tion by uti­liz­ing a nov­el sig­nal­ing path­way dif­fer­ent from any cur­rent­ly avail­able immunother­a­py. Such data pro­vide proof of con­cept that the ratio­nal design of immunos­tim­u­la­to­ry agents, dif­fer­ent from cur­rent­ly avail­able check­point inhibitors or cytokines, may extend the range of ther­a­peu­tic options avail­able to can­cer patients. The pre­clin­i­cal research found that in both murine and human CD8+ T cells, OPL-0101 improved CD8+ T cell via­bil­i­ty increased mem­o­ry cell gen­er­a­tion, and decreased exhaus­tion. This appears to be the result of the aug­men­ta­tion of T cell recep­tor sen­si­tiv­i­ty and acti­va­tion of the Nuclear Fac­tor of Acti­vat­ed T Cells (NFAT) path­way of T cell acti­va­tion. Valo believes that OPL-0101 thus offers the poten­tial to enhance T cell recep­tor recog­ni­tion of low-affin­i­ty anti­gens, such as can­cer neoanti­gens, as a mech­a­nism to over­come tumor immu­no­eva­sion. In mul­ti­ple murine pre­clin­i­cal mod­els as well as CAR-mod­i­fied human T cells, tar­get­ing of CD19 express­ing malig­nan­cies OPL-0101 out­per­formed both IL2 and IL-15 for tumor con­trol. Impor­tant­ly OPL-0101 syn­er­gized with anti-CTLA4 immunother­a­py to pro­vide a long-term cure of murine lung cancer.

Alexan­der Sasha Krup­nick, MD, Chief of Tho­racic Surgery and Sur­gi­cal Direc­tor of the Lung Trans­plant Pro­gram at the Uni­ver­si­ty of Mary­land School of Med­i­cine, and the senior author of the study and co-inven­tor of the tech­nol­o­gy behind OPL-0101, said that the study shows the val­ue of the unique tumor-tar­get­ing can­di­date OPL-0101.

I believe that the research high­lights OPL-0101 as a poten­tial new ther­a­peu­tic agent in immunother­a­py, whose biol­o­gy and mech­a­nism of action is dis­tinct from cur­rent­ly avail­able check­point inhibitors and cytokines,” said Krup­nick who is a con­sul­tant to Valo. This agent rep­re­sents a new class of bio­log­ic agents which will aim to form the basis of future nov­el mul­ti­modal­i­ty ther­a­py for mul­ti­ple malignancies.”

OPL-0101 is a pro­tein ther­a­peu­tic design for cell tar­get­ing and to dri­ve spe­cif­ic bio­log­i­cal respons­es in tar­get­ed cells. Valo acquired the exclu­sive license to OPL-0101 when it acquired Couri­er Ther­a­peu­tics in 2021. The intent of the under­ly­ing design of OPL-0101 is to enable pro­fes­sion­al killing cells to tar­get can­cers with reduced tox­i­c­i­ty. The orig­i­nal research and design of OPL-0101 was done by Dr. Krup­nick and team at Wash­ing­ton Uni­ver­si­ty in St. Louis, where the team sought to har­ness the sig­nal­ing prop­er­ties of a unique cytokine by design, where T cell sur­face bind­ing and sig­nal­ing are sep­a­rat­ed between two dif­fer­ent fam­i­lies of recep­tors. This fusion pro­tein cytokine binds with high affin­i­ty to the cyto­tox­ic lym­pho­cyte-defin­ing immunore­cep­tor NKG2D but sig­nals through the com­mon γ‑chain cytokine recep­tor. Such ratio­nal design of sep­a­rat­ing the bind­ing acti­vat­ing recep­tors vir­tu­al­ly elim­i­nates off-tar­get side effects which remain the main bar­ri­er to broad­er use of immunos­tim­u­la­to­ry agents.

In addi­tion to pre­cise acti­va­tion of cyto­tox­ic lym­pho­cytes due to NKG2D bind­ing, the research describes that OPL-0101 results in supe­ri­or acti­va­tion of both human and murine CD8+ T cells by improv­ing their sur­vival, mem­o­ry cell gen­er­a­tion, and decreas­ing exhaus­tion. This func­tion­al improve­ment appears to be the result of altered sig­nal trans­duc­tion based on the reor­ga­ni­za­tion of sur­face mem­brane lipid rafts that lead to Janus Kinase‑3 (JAK3)-mediated phos­pho­ry­la­tion of the T cell recep­tor (TCR) rather than STAT/AKT sig­nal­ing inter­me­di­ates. The nov­el sig­nal­ing path­way acti­vates Nuclear Fac­tor of Acti­vat­ed T Cells (NFAT) tran­scrip­tion fac­tor, lead­ing to increased mito­chon­dr­i­al bio­gen­e­sis, and increased CD8+ T cell respons­es to low-affin­i­ty anti­gens, cre­at­ing an oppor­tu­ni­ty to specif­i­cal­ly cat­alyze activ­i­ty against can­cer neoantigens. 

About Valo Health

Valo Health, Inc (“Valo”) is a tech­nol­o­gy com­pa­ny built to trans­form the drug dis­cov­ery and devel­op­ment process using human-cen­tric data and arti­fi­cial intel­li­gence dri­ven com­pu­ta­tion. As a dig­i­tal­ly native com­pa­ny, Valo aims to ful­ly inte­grate human-cen­tric data across the entire drug devel­op­ment life cycle into a sin­gle uni­fied archi­tec­ture, there­by accel­er­at­ing the dis­cov­ery and devel­op­ment of life-chang­ing drugs while simul­ta­ne­ous­ly reduc­ing costs, time, and fail­ure rates. The com­pa­ny’s Opal Com­pu­ta­tion­al Plat­form is an inte­grat­ed set of capa­bil­i­ties designed to trans­form data into valu­able insights that may accel­er­ate dis­cov­er­ies and enable Valo to advance a robust pipeline of pro­grams across car­dio­vas­cu­lar meta­bol­ic renal, oncol­o­gy, and neu­rode­gen­er­a­tive dis­ease. Found­ed by Flag­ship Pio­neer­ing and head­quar­tered in Boston, MA, Valo also has offices in San Fran­cis­co, CA, New York, NY, Lex­ing­ton, MA, and Bran­ford, CT. To learn more, vis­it www​.val​o​health​.com.

Investors: Graeme Bell, Chief Finan­cial Offi­cer gbell@ val­o­health. com