Interim Results from Phase 1b/2 ACE-MM-102 and Phase 1a/1b ACE-MM-200 Studies to be Presented at the 57th Annual Meeting of the American Society of Hematology

Boston (Press Release) Acetylon Pharma­ceu­ticals, Inc., the leader in the devel­op­ment of selective histone deacetylase (HDAC) inhibitors for en­hanced thera­peutic out­comes, today announced that it will present clin­i­cal data demonstrating promising tolerability and over­all response rates from a Phase 1b/2 study of a selective HDAC6 inhibitor, ricolinostat (ACY-1215), in com­bi­na­tion with poma­lido­mide (Pomalyst^®, Celgene) and dexa­meth­a­sone for the treat­ment of re­lapsed-and-refractory multiple myeloma (ACE-MM-102 study). These data will be presented in a poster presentation this evening from 6:00pm to 8:00pm EST at the American Society of Hematology (ASH) Annual Meeting in Orlando, Florida. In addi­tion, pre­lim­i­nary results from the Phase 1a/1b ACE-MM-200 study investigating the safety of ACY-241, a structurally related analog of ricolinostat, in com­bi­na­tion with poma­lido­mide and dexa­meth­a­sone in patients with re­lapsed or re­lapsed-and-refractory multiple myeloma were presented in a poster session on Sunday, December 6 at the ASH Annual Meeting.

“The data from both the 102 study with ricolinostat and the 200 study with ACY-241 dem­onstrate that selective HDAC6 inhibition combines favorably with poma­lido­mide and dexa­meth­a­sone, and we believe this ap­proach has the poten­tial to become a powerful treat­ment option for patients with re­lapsed or refractory multiple myeloma while having minimal side effects that are commonly seen with pan-HDAC inhibition,” said Catherine Wheeler, SVP Clinical Development & Chief Medical Officer of Acetylon. “The promising activity profile of ricolinostat reported for the earlier portions of the 102 trial has been maintained in the Phase 2 portion. At a planned interim analysis of patients refractory to their most recent ther­apy and followed for at least six months, the over­all response rate (ORR) was greater than 50%. Further­more, the ORR rate was similar for those patients who were pre­vi­ously refractory to lena­lido­mide (Revlimid^®, Celgene) or bor­tez­o­mib (Velcade^®, Millennium), or who have high risk disease cytogenetics (17p deletion and/or 4:14 translocation). Minimal toxicity was asso­ci­ated with once daily admin­istra­tion of ricolinostat or ACY-241, and no dose-limiting toxicities have been observed in either study to-date.”

The Phase 1b/2 ACE-MM-102 clin­i­cal trial is a multi­center, open-label, dose escalation study designed to determine the maximum tolerated dose, safety, and efficacy of ricolinostat in com­bi­na­tion with poma­lido­mide and dexa­meth­a­sone in patients with re­lapsed-and-refractory multiple myeloma. Preliminary data from this study indicate that selective HDAC6 inhibition in com­bi­na­tion with poma­lido­mide and dexa­meth­a­sone is well tolerated, with no dose-limiting toxicities observed to-date. The most common adverse events were fatigue, diarrhea and hema­to­logic toxicity, and most were low grade and not asso­ci­ated with ricolinostat. Diarrhea initially observed with twice-daily dosing of ricolinostat was less frequent after a recommended oral dose of 160 mg once daily for 21 days of a 28 day cycle was identified. A planned interim analysis dem­onstrates promising clin­i­cal activity for 30 evaluable patients having at least 6 months of follow up, in­­clud­ing a con­firmed over­all response rate (defined as a partial response or better) of 53%, a clin­i­cal benefit rate (defined as minimal response or better) of 63%, and a disease control rate (defined as stable disease or better) of 90%.

ACY-241 is a structurally related, orally avail­able selective HDAC6 inhibitor admin­istered in tablet form. A Phase 1a/1b clin­i­cal trial, ACE-MM-200, was ini­ti­ated to determine the maximum tolerated dose, safety, and pre­lim­i­nary anti-tumor activity of ACY-241 alone and in com­bi­na­tion with poma­lido­mide and dexa­meth­a­sone in patients with re­lapsed or re­lapsed-and-refractory multiple myeloma. A sequential mono­therapy/​combi­na­tion trial design allows patients access to com­bi­na­tion ther­apy based on an estab­lish­ed regi­men starting in the second cycle of treat­ment, while estab­lish­­ing the safety, pharmaco­kinetics, and pharmaco­dynamics of ACY-241 as both a mono­therapy and in com­bi­na­tion. Preliminary results indicate that ACY-241 is well tolerated as a mono­therapy and in com­bi­na­tion with poma­lido­mide and dexa­meth­a­sone, and no dose-limiting toxicities have been observed in either case. The most common adverse events for ACY-241 mono­therapy were low grade nausea and hema­to­logic toxicity, while the most common adverse events for the com­bi­na­tion regi­men were low grade fatigue and hema­to­logic toxicity. As a mono­therapy, ACY-241 has dem­onstrated a dose-proportional in­­crease in exposure from 180 mg (Cohort 1) to 360 mg (Cohort 2), and exposure at the 180 mg dose level surpassed exposure for ricolinostat at the clin­i­cal dose of 160 mg. Preliminary evi­dence of anti-tumor activity was observed, although most evaluable patients had received only 1-3 cycles of treat­ment at the time of analysis.

“These promising interim results from our ricolinostat and ACY-241 trials in multiple myeloma are build­ing a strong rationale for ad­vancement of our HDAC6 selective inhibitors pro­gram to the pivotal phase of clin­i­cal devel­op­ment over the coming year,” said Walter C. Ogier, Pres­i­dent and Chief Executive Officer of Acetylon. “We also look forward to publishing the com­pleted results of these studies and to the near term initiation of several new com­pany- and investigator-sponsored clin­i­cal trials exploring com­bi­na­tions of our HDAC6 inhibitor drug can­di­dates with addi­tional, estab­lish­ed drug regi­mens for patients with hema­to­logic and solid tumor cancers.”

Details of the presentations are as follows:

Date: Sunday, December 6, 2015

Time: 6:00 PM-8:00 PM

Location: Hall A, Level 2 (Orange County Convention Center)

Session: 653. Myeloma: Therapy, excluding Transplantation: Poster II

Abstract Number: 3040

Title: ACY-241, a Novel, HDAC6 Selective Inhibitor: Synergy with Immunomodulatory (IMiD®) Drugs in Multiple Myeloma (MM) Cells and Early Clinical Results (ACE-MM-200 Study)

Date: Monday, December 7, 2015

Time: 6:00 PM-8:00 PM

Location: Hall A, Level 2 (Orange County Convention Center)

Session: 653. Myeloma: Therapy, excluding Transplantation: Poster III

Abstract Number: 4228

Title: Ricolinostat (ACY-1215), the First Selective HDAC6 Inhibitor, Combines Safely with Pomalidomide and Dexamethasone and Shows Promising Early Results in Relapsed-and-Refractory Myeloma (ACE-MM-102 Study)

About HDAC6 Inhibition

Ricolinostat (ACY-1215) and ACY-241 selectively inhibit the intracellular enzyme HDAC6, which leads to an accumulation of excess protein and in addi­tion may disrupt critical proliferative signals in malignant cells. Disruption of these molecular processes in cancer cells triggers pro­grammed cell death, called "apoptosis," with little or no effect on normal cells. Currently avail­able HDAC drugs also affect the ex­pres­sion of numerous other genes in normal cells as well as cancer cells, which can result in side effects such as gastro­in­tes­ti­nal dysfunction, lowered blood platelet levels and risk of hemorrhage and profound fatigue as well as poten­tial for sig­nif­i­cant cardiac toxicity. Selective inhibition of HDAC6 is ex­pec­ted to reduce or elim­i­nate these often-severe side effects asso­ci­ated with non-selective HDAC inhibition and may enable the devel­op­ment of optimized treat­ment regi­mens, in­­clud­ing maximally effective com­bi­na­tion drug ther­a­pies.

About Acetylon

Acetylon Pharma­ceu­ticals, Inc., based in Boston, Massachusetts, is a leader in the devel­op­ment of novel small molecule drugs targeting epigenetic mech­a­nisms for the en­hancement of thera­peutic out­comes in cancer and other critical human diseases. The Company’s epigenetic drug discovery plat­form has yielded a pro­pri­e­tary portfolio of optimized, orally-administered Class I and Class II histone deacetylase (HDAC) selective com­­pounds. Alteration of HDAC reg­u­la­tion through selective HDAC inhibition is thought to be appli­­cable to a broad range of diseases in­­clud­ing cancer, sickle cell disease and beta-thalassemia, and auto­immune and neurodegenerative diseases. Acetylon’s lead drug can­di­date, ricolinostat (ACY-1215), is a selective HDAC6 inhibitor cur­rently in Phase 2 clin­i­cal devel­op­ment for the treat­ment of multiple myeloma. In 2013, the Company announced a strategic col­lab­o­ration agree­ment with Celgene Corpo­ra­tion, which in­cludes an exclusive option for the future acquisition of Acetylon by Celgene. Acetylon’s scientific founders are affiliated with Harvard University, the Dana-Farber Cancer Institute, the Massachusetts General Hospital, and Harvard Medical School. www.acetylon.com

Source: Acetylon.