Locus Pharmaceuticals has inked separate research agreements with a pair of University of Texas System institutions to advance a portfolio of preclinical anti-cancer drug candidates, the company said last week.
Although the collaborations, with the UT Health Science Center, San Antonio, and the MD Anderson Cancer Center in Houston, are distinct, their common goal to develop treatments for cancers characterized by inflammation and angiogenesis means that the projects could at some point converge, a company official said this week.
“We have two different compounds that we think are uniquely positioned, and that is why we’re quite pleased with the ability to have this interaction with two very credible centers and groups that are highly motivated,” Joseph Riser, president and CEO of Locus, told BTW this week.
“There will be interaction and discussion, I suspect, between the two groups, but they both have their own areas of expertise within this field, and they both have their own approaches and models,” Reiser added. “You never know in these things — it may evolve to be part of the same study.”
Locus, based in Blue Bell, Pa., specializes in using computational drug design to generate oral drug candidates primarily in the areas of cancer and inflammation. According to the company, it has used this approach both to develop its own compounds and to support drug-development partnerships with pharmaceutical, government, and academic partners.
Under one of the research agreements announced last week, Locus will tap the laboratory of Francis Giles, director of the Institute for Drug Development, part of the Cancer Therapy and Research Center at UTHSCSA.
Specifically, Giles’ lab will investigate the anti-angiogenic and anti-inflammatory potential of compounds in Locus’ p38 portfolio, which comprises highly selective allosteric inhibitors of p38 alpha and beta isozymes; and LP-590, a multikinase inhibitor of p38, Tie-2, and Ret kinases.
Giles told BTW that in particular, the drugs show promise as potential treatments for hematological malignancies such as multiple myeloma; ovarian cancer; and certain types of breast cancer.
“We’re very excited about the potential for this target across a number of cancers, and specifically across a number of cancers where we’re pretty desperate for targeted therapy,” Giles said.
“We are looking for a pattern of inflammation and angiogenesis as critical drivers of the pathophysiology,” Giles added. “The ways to define that and the ways to look at it are becoming more and more refined. What excites us is that [Locus] has good technology, they seem to be able to deliver clean drugs to us, and we’re very familiar with this overall group of drugs.”
Elaborating on the latter point, Giles stressed that the large body of existing work in the areas of non-cancerous inflammatory and immune conditions — in particular “a reasonably large body of data about the target, and what happens when you inhibit it” — makes Locus’ p38 portfolio of compounds especially ripe for development into anti-cancer drugs.
“You don’t usually have … a very high degree of prior information on safety, what to look for and what to avoid, with a target that is clearly of major relevance,” Giles said. “We don’t have to go blind fishing, so to speak, in terms of relevant histologies.”
Locus’ agreement with CTRC builds upon an existing research relationship that focuses on the company’s lead clinical candidate, LP-261, an oral tubulin inhibitor that has shown broad anti-tumor activity in preclinical models and is currently in Phase I clinical trials.
“We’re very excited about the potential for this target across a number of cancers, and specifically across a number of cancers where we’re pretty desperate for targeted therapy.”
Although this project with CTRC is unrelated to the newest collaboration, it helped set the tone for additional collaborations, Giles said.
“We have a Phase I study and other studies ongoing with [Locus], and it’s reasonable to say that we have initial information that we’re excited about, and that we’re satisfied with the integrity of the company as an entity to deal with,” Giles said.
The existing studies are being conducted under a traditional sponsored research agreement between Locus and CTRC. However, the most recent agreement will follow a slightly different tack in that CTRC plans to fund the majority of the research on its own through typical academic research grants.
“We’re excited enough that not all of this is sponsored research,” Giles said. “We’re going to do pure academic work on our own dollar, our own grants, because we think this is a major way to go forward.”
Reiser added that although Locus couldn’t disclose specific funding terms, “it’s definitely not a CRO relationship. It is a true collaborative relationship with intrinsic interest from both parties. We have to supply the drug, and provide certain things, and will do that to enhance the project. But they will, on their own, invest in the collaboration because they have a strong interest.”
However, unlike the LP-261 collaboration, which is essentially in the clinical phase, the p38 agreement could result in the development of intellectual property that UTHSCSA would own and that may be of interest to Locus down the road.
“At this point, there is no IP transfer from our point of view,” Reiser said. “If something new were to come out, we would certainly consider it, as is usual in these types of collaborations.”
Giles added that he is “very confident” that the project will generate meaningful IP, and that UTHSCSA already owns “synergistic” IP developed by Tyler Curiel, executive director of CTRC and another participant in the research project.
Locus’ collaboration with MD Anderson will be conducted at the institute’s Morgan Welch Inflammatory Breast Cancer Research Program and Clinic, and led by Massimo Cristofanilli, director of the clinic; and Fredika Robertson, a professor of experimental therapeutics at MD Anderson.
This research project is more specific in nature than the UTHSCSA alliance, and will study whether and to what extent the multikinase inhibitor LP-590 can treat inflammatory breast cancer, Locus said.
As such, Locus is “supporting that project a little bit more because we really wanted the answer on that,” Reiser said. “But it’s only the first step, we think, of a broader relationship with MD Anderson.”
Reiser added that MD Anderson was an attractive partner for this project because of the institute’s specific expertise in inflammatory breast cancer. “They are probably the leading group in that regard,” he said.
In a statement, Cristofanilli and Robertson said that “inflammatory breast cancer is a very aggressive type of breast cancer that can be resistant to standard therapies. LP-590, in particular, is of great interest to us because of the potential importance of both p38 and Tie-2 in this variant of breast cancer.”
Detailed financial terms of this agreement were not disclosed, and it is unclear whether the project might result in the development of IP that would be of potential interest to Locus.
It is also unclear exactly how closely MD Anderson’s Cristofanilli, Robertson, and others will work with researchers at UTHSCSA on the Locus projects. Calls to MD Anderson’s external communications office were not returned in time for this publication.
However, according to Reiser, the projects will remain separate at the outset, but share enough in common that an overlap is possible. “In one case it is a selective target, and in the other it is a multi-kinase target, but they obviously share properties such that they each could be considered in both approaches,” Reiser said.
“We have had discussions jointly in this regard, and they know of each others’ work,” he added. “If there is an opportunity to synergize the two groups, then we will do that.”
Giles added that as sister UT system institutions, “there is plenty of room for future collaboration” between researchers at UTHSCSA and MD Anderson on the Locus projects, but that the individual projects are not joined presently.
Even if a three-way collaboration doesn’t materialize, from Locus’ point of view the research projects are inextricably linked due to the status of the compounds involved.
“Most important is the timing of these interactions, because we are in a late-stage pre-clinical phase with both of these programs, and these types of studies will very much help guide the thinking in terms of the clinical strategy,” Reiser said.