The American Society of Hematology’s annual meeting (56th!) begins on December 6, but abstracts from the conference will be released this morning. This, and the release of late-breaking abstracts on November 17, are much-watched events for healthcare investors given the plethora of potentially market-moving data to be revealed publicly for the first time.
We’ve collated some of the bigger data events to look for today and in the next month. It’s never entirely clear what will be contained in each abstract vs. what will be presented at the meeting, but these are some of the more important names to keep on your radar.
Merck (MRK) and Bristol-Myers Squibb (BMY): Big Pharma’s anti-PD-1 Assets in Hematologic Malignancies
Merck and Bristol-Myers Squibb are both expected to present data from ongoing trials with their respective PD-1 inhibitors in hematologic malignancies. Investors have been anxiously awaiting these data to determine if PD-1 inhibitors provide the same, impressive clinical benefit in blood cancers that they do in solid tumor indications (namely, melanoma). As anti-PD1 trials in blood cancers mature and reach completion over the next few years, investors will be watching closely to determine which drug has best-in-class efficacy and potential to be first to approval in this yet untouched market. Today’s results may be the first hint.
Merck is expected to present interim Keytruda (Pembrolizumab; data anti-PD-1) data from the KEYNOTE-013 study in individuals diagnosed with hematologic malignancies. KEYNOTE-013 has a primary completion date of December 2015 and includes patients with Myelodysplastic Syndrome, Multiple Myeloma (MM), Hodgkin’s (HL), and Non-Hodgkin’s Lymphomas (NHL).
Bristol Myers is also expected to present data on Opdivo (Nivolumab; anti-PD-1) from the ongoing phase I CHECKMATE-039 study – also patients diagnosed with hematologic malignancies (HL, NHL, MM). BMY will present interim data from monotherapy cohorts at ASH, and the company could potentially present Nivolumab + Yervoy combination data from this study.
TG Therapeutics (TGTX): TG-1101 and 1202
A meaningful number of patients with B-cell malignancies continue to come off standard-of-care drugs such as ibrutinib (BTK inhibitor), rituximab (anti-CD20 mAb), and idelalisib (PI3Kδ inhibitor) due to progressive disease (lack of efficacy) or toxicity. TG Therapeutics is positioning itself to capture a portion of this market, leveraging TG-1101 (glyco-engineered anti-CD20 mAb) and TGR-1202 (PI3Kδ inhibitor). Investors are looking to TG Therapeutics to present more efficacy and safety data for TG-1101 and TGR-1202. Most important are data validating the company’s combination strategy: testing ibrutinib, TG-1101, and TGR-1202 together in individuals with B-cell malignancies. TG Therapeutics is expected to present datasets from 3 ongoing trials of TG-1101 and TGR-1202:
- TG-1101 (anti-CD20) + Ibrutinib (BTK inhibitor) combo data
- This data builds upon previously presented results at EHA demonstrating an overall response rate (complete response + partial response) of 100% in subjects with mantle cell lymphoma (MCL, 1/3 CR; 2/3 PR) and 86% in subjects with chronic lymphocytic leukemia (CLL, 6/7 PRs). At first assessment, this data compares favorably to ibrutinib as a single agent.
- In the updated data from this trial at ASH, investors will be looking for high (>80%) ORR in MCL and CLL, as well as the asset’s tolerability profile.
- TG-1101 (anti-CD20) + TGR-1202 (PI3Kδ inhibitor) combo data
- Data presented at ASH will build upon previously presented data at the Pan Pacific Lymphoma conference demonstrating the combination to be well tolerated, with an ORR of 6/15 (6 PRs).
- Investors will be looking at tolerability and an improving response rate over time.
- TGR-1202 (PI3Kδ inhibitor) phase I monotherapy in relapsed/refractory hematologic malignancies:
- This incremental update follows data at EHA earlier this year validating in-part the clinical efficacy and safety of TGR-1202. The EHA update also included PK data from new fed-state and micronized TGR-1202 dosing. These new dosing schedules could provide improved efficacy at a lower dose. Investors are looking for similar efficacy to Gilead’s (GILD) idelalisib, with potentially better safety. This would be a positive readthrough on TGR-1202’s ability to be combined with other B-cell signal modulating drugs (like ibrutinib and anti-CD20s).
As discussed above, these trials are designed to validate the TG-1101, TGR-1202, and ibrutinib combination strategy in B-cell malignancies. Tolerability may be the limiting issue: combination therapy (BTK inhibitors, CD20s, PI3Ks) has thus far remained elusive. We note that Gilead’s Idelalisib was approved with a black box warning, and has – arguably – been a commercial disappointment because of intolerable side effects.
Agios Pharmaceuticals (AGIO): AG-221
Agios is expected provide an update on the ongoing phase I dose escalation study of AG-221 (IDH2m inhibitor) in advanced hematologic malignancies. Preliminary data from this trial was presented at EHA in June, which we wrote about here. Expectations for Agios are already high; Agios is a $2.8 billion company based on early, phase I data (promising data, to be sure) from the company’s pipeline. If updated results fall short of investor expectations, look for the stock to correct significantly.
Epizyme (EPZM): Better Look at HMT program (DOT1L inhibitor)
Epizyme is developing novel histone methyltransferase (HMT) inhibitors for the treatment of hematologic cancers, the company will present new EPZ-5676 clinical data at ASH. The company’s lead HMT inhibitor asset, the EZH2 inhibitor EPZ-6438, has already generated clinically validating data in a number of hematologic malignancies.
Epizyme presented preliminary -5676 data from an ongoing phase I trial in patients diagnosed with leukemias (including those with MLL-rearrangement) at ASH in 2013, demonstrating 2 objective responses in a later cohort (fourth, 54 mg/m2/day). Epizyme is planning to present dose-escalation and MLL-r expansion stage proof-of-concept data from this trial at ASH this year. In addition, Epizyme is planning to present PK modeling data for EPZ-5676 in MLL-r pediatric subjects at ASH. Investors will be looking for additional efficacy signals from EPZ-5676, continued validation of the company’s HMT program.
Bluebird Bio (BLUE) and LentiGlobin in ß-thalassemia
Bluebird bio is guiding to present additional data from their gene therapy product LentiGlobin in ß-thalassemia patients by the end of 2014. Due to the timing of the data guidance, and ß-thalassemia being a hematological disease, some investors are expecting to see data at ASH from the ongoing phase I/II NORTHSTAR and HGB-205 trials.
If bluebird does present at ASH, it may be in a late breaking abstract, which would be released November 17. We have discussed bluebird and outlined our expectations for the ß-thalassemia release here.
Geron (GERN) and Imetelstat
Geron is guiding to present updated and additional imetelstat data from their ongoing phase II Myelofibrosis IST trial this year. Preliminary data from this trial, presented at ASH 2013, demonstrated an overall response rate (complete response + partial response) in 5/22 subjects, unprecedented in this indication.
As a reminder, a full clinical hold was placed on the imetelstat program following hepatotoxicity observed in company-sponsored phase II trials. This full clinical hold was lifted on November 3 (discussed here), and the company no longer plans to continue development in some of their initial, planned indications.
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Karyopharm (KPTI) and SINE
Karyopharm is expected to present updated selinexor clinical data at ASH from at least 2 ongoing trials: a phase I trial in multiple myeloma in combination with dexamethasone, and an update from the DLBCL cohort of the phase I dose-finding trial of selinexor in individuals with advanced hematologic malignancies.
Selinexor is a Selective Inhibitor of Nuclear Export (SINE). More specifically, selinexor is an exportin 1 (XPO1) inhibitor which induces the nuclear localization of tumor suppressor proteins such as p53 in order to reduce levels of proto-oncogenes and induce apoptosis. Karyopharma presented impressive initial selinexor data at EHA earlier this year: an overall response rate of 6/24 (1 CR, 5 PRs) in the DLBCL cohort, and an overall response rate of 4/8 (1 sCR, 3PRs) in subjects enrolled in the selinexor + low dose dexamethasone cohort of the multiple myeloma trial. Investors will look for these to remain durable and possibly be seen in a wider patient population.
Kite Pharma (KITE) and the Chimeric Antigen Receptor T Cell (CAR-T) Gang
Kite Pharma is expected to provide an incremental update on diffuse large B-cell lymphoma (DLBCL) patients enrolled in their KTE-C19 (anti-CD19 CAR-T) phase I/IIa study in individuals with advanced B-cell malignancies. This data is expected to build upon previously published Non-Hodkin’s Lymphoma KTE-C19 data, demonstrating an overall response rate of 12/13 (8 CR, 4PR). In DLBCL patients evaluable for response, the overall response rate was 6/7 (4 CR, 2 PR). We will look for KTE-C19 to continue to demonstrate robust (CRs) and durable responses in DLBCL. Positive data would validate Kite’s leadership in CAR-T for DLBCL.
The ASH Annual Meeting may also highlight new preclinical or clinical data from other companies or organizations working on CAR-Ts. We will be looking for new data potentially from Novartis (NVS) and UPenn, Cellectis (partnered with Pfizer [PFE]), Juno Therapeutics (private), or Adaptimmune (partnered with GlaxoSmithKline [GSK]).
CD47 watch
We will be on the lookout for any new data emerging from either Stanford or Celgene’s CD47 programs. As we wrote here, CD47 inhibition will be a story to watch in 2015.
Seattle Genetics is expected to present data from ongoing trials with Adcetris, SGN-CD33A, and SGN-CD19A at the meeting. Seattle Genetics will be presenting a number of datasets from ongoing trials of Adcetris in Hodkin’s Lymphoma (HL) and DLBCL. It’s important for SGEN to demonstrate strong results in HL to avoid changing perceptions of Adcetris’ spot in the HL space if anti-PD-1s are as compelling in the indication; these data are expected at ASH. Note, however, that in the long-run the threat to Adcetris from immunotherapies may be moot (in our view) – the future of cancer treatment is truly in combination treatments.
One or more of PropThink’s contributors are long MRK, BMY, TGTX, BLUE, ALCLS.PA or SCTPF.
