Jatin Shah, MD of Sumitomo Pharma, discusses two treatments in Phase 1 trials for myelofibrosis and acute myeloid leukemia, aggressive diseases that impact the body’s normal production of blood cells.

Transcription:
My name is Jatin Shah. I'm an oncologist by training and spent about 10 years at MD Anderson Cancer Center for about 10 years before I joined Sumitomo, and I'm currently the Chief Oncology Development Officer at Sumitomo. I'm excited here really to talk about several products that were in development phase in our phase 1 trials that were just recently presented at [inaudible 00:00:27].

Just as a quick introduction to Sumitomo, you may not have heard of Sumitomo, and many folks may not have heard of us, but in fact, Sumitomo has been around for greater than 400 years with a longstanding history in pharmaceutical drug development outside of oncology, including rare diseases. We've been focused in the oncology space for the last 10 to 15 years with research and development.

Myelofibrosis belongs to a group of diseases called myeloproliferative disorders. This includes other diseases like polycythemia vera or essential thrombocythemia. It's a serious bone marrow disorder, but also a rare bone marrow disorder that impacts the body's normal production of blood cells.

The typical age for patients who see this is going to be our older patients above the age of 60 or 65. There's a slightly higher incidence of prevalence in males compared to females, but there are no other established risk factors that we're aware of.

There may be several symptoms. A, patients may be completely asymptomatic, with no symptoms at all, it will just be picked up on routine blood work, or if they do have symptoms, it will include two main things.

One is splenomegaly, which is an increase in the size of the spleen. As your disease progresses, that spleen increases in size and can be quite large and have a lot of symptoms, including abdominal discomfort. The second is something we call constitutional symptoms, which is a constellation of symptoms including fatigue, night sweats, lowgrade fevers, and weight loss.

If you have something called lowrisk disease, those are patients who are typically asymptomatic at diagnosis, and observation is a typical approach for those patients.

However, as you start developing symptoms, or you have some highrisk features, you'll be treated with one of two main ways. One is an allogeneic bone marrow transplant, which is a bone marrow transplant for stem cells using a donor. The second is JAK inhibitors. The JAK inhibitors have been a mainstay of therapy in the US for the last decade plus.

What we know is that TP3654 is an oral investigational inhibitor or selective inhibitor of PIM1 kinase. Now, why is that important? One, because we know that PIM1 is significantly elevated in patients with myelofibrosis in their bone marrow, in their hematopoietic, or their stem cells. We know that elevated PIM1 in the published data contributes to the cancer activation, cytokine modulation, which are these no inflammatory proteins or cytokines through multiple pathways.

Then in our preclinical work, we've shown that if we can inhibit PIM1 with 3654 in mouse models and other preclinical models, we assume that we can reduce cytokines, inhibit this proliferation or growth of these cancer cells, and lead to apoptosis or death of these cancer cells.

Additionally, we've seen in mouse models that with 3654, we can reduce the spleen size and improve the bone marrow fibrosis in these mouse models. This body of data now in the preclinical setting is the data that supports the phase 1 ongoing clinical trial.

The intent of this trial was to look at monotherapy or single agent 3654 in patients with intermediate or highrisk myelofibrosis who had been previously treated or ineligible for a JAK inhibitor. In this patient population, we've now used escalating doses of 3654, and shown one of several things.

Number one, we've shown that it's well tolerated with limited myelosuppression or limited drops in their blood counts. That's important because a lot of our cancer therapies can cause drops in their blood counts. We've shown that the side effects now is going to be predominantly nausea, and vomiting, and diarrhea, which are with lowgrade, and with prophylactic therapy, can be managed.

Now we're getting to what we think is the right dose of 3654, and now we've started seeing early signals of clinical activity with reductions in splenic volume, as well as improvements in the symptom burns. Those are two key measures we look at how to identify if a drug works in myelofibrosis...

Chapters:
00:00 Intro
00:50 Myelofibrosis Overview
3:12 How Does TP3654 Work?
4:30 TP3654 Phase 1 Clinical Trial
5:59 Next Steps for TP3654
6:38 Acute Myeloid Leukemia Overview
7:53 How Does DSP5336 Work?
9:39 Next Steps for DSP5336