Things may soon be looking up for liposomal anthracycline L-annamycin, in the works for acute myeloid leukemia (AML), if Moleculin Biotech Inc. has anything to say about it.

Houston-based Moleculin priced its IPO to sell at least 1.4 million and as many as 2 million shares at $6 each, for a top range of $12 million, and the money from the pending deal will go partly to apply for an investigational new drug (IND) application for the compound. Rights came to Moleculin in October from Annamed Inc., also of Houston, for an undisclosed sum. Moleculin wants to audit a previously conducted phase I/II trial, nail down a special protocol assessment with the FDA and start a phase II experiment with L-annamycin.

Moleculin was founded in 2015 by Walter Klemp, the firm's chairman and CEO; Don Picker, president and chief operating officer; and Waldemar Priebe of MD Anderson Cancer Center. After picking up the rights to L-annamycin, the firm licensed the WP1122 portfolio from Intertechbio Corp., also of Houston. Yet another outfit in the city, Houston Pharmaceuticals Inc., has been the subject of co-development talks regarding its WP1066 portfolio.

The program with WP1122 aims to exploit the metabolic differences between tumor cells and normal cells, with a lead candidate targeted specifically for metabolically active brain cancers, taking advantage of the differences in the way cancerous tissue uses glucose as compared to normal brain tissue. Prospects undergoing research have shown encouraging activity in vitro and in an animal model's implanted tumor, the firm said. One drug hopeful even seemed to surpass Kenilworth, N.J.-based Merck & Co. Inc.'s strong-selling Temodar (temozolomide).

With WP1066, Moleculin is targeting signal transducers and activators of transcription – the oncogenic transcription factors known as STATs – which play an important role in disease-cell survival and proliferation, angiogenesis and immune system function.

L-annamycin, though, is furthest along, having fallen into the hands of Annamed from Callisto Pharmaceuticals Inc., of New York, which disclosed in a 2009 SEC filing that the leukemia results with the compound "did not support further clinical evaluation of L-annamycin as a single agent to treat relapsed or refractory adult acute leukemia patients." In order to satisfy unmet license obligations, Callisto agreed to transfer all available annamycin data to Annamed – data that Moleculin now will use to apply for the new IND. In its own filing related to the IPO, Moleculin said the outcomes gleaned so far and reported by Moleculin's chief medical officer (CMO), Robert Shepard (who was previously Callisto's CMO), at the 2009 American Society of Clinical Oncology (ASCO) meeting do indeed "support further clinical evaluation."

What's more, the conclusion published in 2013 in Clinical Lymphoma, Myeloma & Leukemia found that "single-agent nanomolecular L-annamycin appears to be well-tolerated and [shows] evidence of clinical activity as a single agent in refractory adult acute lymphocytic leukemia." Efficacy at the ASCO presentation and in the journal article was based on response criteria that included achievement of complete response (CR) defined as ≤5 percent blasts, granulocyte count of ≥1×109/L and a platelet count of ≥100×109/L. Partial remission was defined the same as CR, except for the presence of 6 percent to 25 percent blasts. Hematologic improvement was defined as for CR but platelet count <100×109/L.

"After determining the maximum tolerated dose [MTD], a 10-patient phase IIa [trial] was conducted," the journal article noted. "Eight of the patients completed one cycle of the three days of treatment at the MTD. Of these, five (62 percent) demonstrated encouraging anti-leukemic activity with complete clearing of circulating peripheral blasts. Three of these subjects also cleared bone marrow blasts with one subsequently proceeding onto successful stem-cell transplantation. The other two developed tumor lysis syndrome and unfortunately expired prior to response assessment." Moleculin's review of the trials found that the activity shown there corresponds with partial remission as described in the response criteria, and that the three subjects who "cleared bone marrow blasts" correspond with CR.

In 2012, Annamed out-licensed development rights in a limited territory to a special-purpose drug development company called Dermin Sp. Zo. O., in Warsaw, Poland, in exchange for Dermin's development work. Dermin had won Polish government grant funding to assist in the development of annamycin, and that money has been used to produce annamycin in preparation for the trials ahead.

In August 2015, Moleculin entered a rights transfer agreement with Annamed whereby, in exchange for about 1.4 million shares of Moleculin stock, Annamed transferred all of its data regarding the development of L-annamycin and the related IND.

The compound has undergone six trials altogether, involving 114 patients, without any reporting of cardiotoxicity and, in the two experiments focused on leukemia, with fewer dose-limiting toxicities than are normally experienced with doxorubicin, one of the leading first-line anthracyclines used for induction therapy. L-annamycin turned up efficacy in eight of 16 patients in a phase I study in adult relapsed or refractory AML patients, with six of 14 patients completely clearing leukemic blasts. A 30-patient dose-ranging phase I/II study in acute lymphocytic leukemia demonstrated a similar efficacy profile, with three of 10 patients treated with the maximum tolerable dose clearing their leukemic blasts to a level sufficient to qualify for a bone marrow transplant. One went on to receive a successfully curative one.

Bonwick Capital Partners LLC and Network 1 Financial Securities Inc. are acting as underwriters for the IPO, after which Moleculin would list on Nasdaq via the symbol MBRX.

Moleculin's was not the only news to provide a glimmer of optimism for others eyeing the public markets. Viamet Pharmaceuticals Holdings LLC, of Durham, N.C., filed amended IPO paperwork with the SEC, saying the company aims to price 5.7 million shares at $14 to $16 each, for a maximum haul of about $104.8 million, and list on Nasdaq under the ticker VMET. (See BioWorld Today, Oct. 22, 2014.)