Bio Path Holdings Inc (BPTH)

[SJSTOCKSHARK]

Crai, Here is the reason for the sell off. I see no NEW info. in the poster.

"1387 Interim Safety and Efficacy of Lower Intensity Induction Therapy with Intravenous Prexigebersen (BP1001) in Patients with Untreated Acute Myeloid Leukemia (AML)


Program: Oral and Poster Abstracts
Session: 613. Acute Myeloid Leukemia: Clinical Studies: Poster I
Hematology Disease Topics & Pathways:
Adult, AML, Diseases, Non-Biological, Therapies, chemical interactions, Biological Processes, Study Population, Clinically relevant, Myeloid Malignancies, signal transduction


Saturday, December 1, 2018, 6:15 PM-8:15 PM

Hall GH (San Diego Convention Center)


Maro N. Ohanian, DO1, Tara L Lin, MD2,3, Ellen K. Ritchie, MD4, Michael Craig, MD5, Apurv Agrawal, MD6*, Kathleen G. Halka, MD7, Vinit Karur, MD7, Naveen Pemmaraju, MD1, Gautam Borthakur, MD1, Sarah Aminov4*, Miranda Lim, BSN8*, Sherry A. Pierce, BSN, BA1*, Natalie Sacarakis9*, Stacy Minor10*, Ana Tari Ashizawa, PhD10, William Hahne, MD10, Hagop M. Kantarjian, MD8, Jorge E. Cortes, MD1 and Gail J. Roboz, MD4

1Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX
2University of Kansas, Westwood, KS
3Division of Hematologic Malignancies & Cellular Therapeutics, University of Kansas, Kansas City, KS
4Weill Cornell Medicine and The Weill Medical College of Cornell University, New York, NY
5West Virginia University, Morgantown, WV
6New Jersey Hematology Oncology Associates, Brick, NJ
7Scott & White Memorial Hospital and Clinic, Temple, TX
8Department of Leukemia, University of Texas M.D. Anderson Cancer Center, Houston, TX
9Novella Clinical, Morrisville, NC
10Bio-Path Holdings, Inc., Bellaire, TX




Background: The growth factor receptor bound protein-2 (Grb2) is vital to tumor progression. Prexigebersen (BP1001) is a liposome-incorporated Grb2 antisense oligonucleotide that inhibits Grb2 expression. Grb2 inhibition suppresses cancer growth and survival. A Phase I/IB single center study (Ohanian, Lancet Haematol 2018) in relapsed/refractory AML patients (pts) demonstrated BP1001 safety up to 90 mg/m2 and demonstrated CR/CRi in 3/6 relapsed/refractory AML pts treated with BP1001 + low dose cytarabine (LDAC) in the Phase IB portion. Based on PK considerations, the recommended Phase II dose was 60 mg/m2. A phase II study was initiated to explore the clinical impact of BP1001 in untreated AML pts considered unsuitable for standard chemotherapy.
Methods: This is a multi-center open-label, Phase II study in untreated AML pts to determine the safety and preliminary efficacy of BP1001 (given at 60 mg/m2 over 1-3 h twice weekly for a total of 8 doses over a 28-day cycle) in combination with LDAC (starting after the Day 4 dose, 20 mg twice daily for 10 days). Eligible pts were considered unsuitable for or refused intensive chemotherapy and had ECOG performance status of 0-2. Blood samples were taken on Days 1 and 11 to determine BP1001 plasma pharmacokinetics (PK).

Results: A total of 25 pts (16 male: 64%) with a median age of 74 years (range, 51-86 years) was treated with at least 1 cycle of BP1001 + LDAC. Sixty-eight percent (17/25) had secondary AML evolved from MDS (n=13) or MPN (n=3) or prior chemotherapy/radiotherapy (n=1). The majority (64%) had adverse-risk (ELN classification); 36% were intermediate-risk. Infusional reactions (IR) (rigors, fevers, or chills) were observed in 20% of pts when the infusion rate was 1 h. IR were mild, controlled with supportive measures, and were not observed when the infusion rate was 2 h. Other AE’s were generally consistent with those expected with LDAC and/or AML, including fatigue (64%), diarrhea (24%), neutropenic fever (24%), and pneumonia (20%). The most frequent SAEs were pneumonia (20%) and neutropenic fever (24%).

Four pts died within 30 days of treatment (between days 20-27), all of AML-related complications (including intracranial hemorrhage, pneumonia, septic shock, and splenic rupture). Ten pts had documented progressive disease. Two pts withdrew consent after 1 cycle of treatment. Evaluability of efficacy was defined as: receipt of at least 4 cycles of therapy, PD, or CR/CRi prior to 4 cycles. PK data revealed that the Time of maximal observed concentration (Tmax), the mean terminal elimination half-life (t1/2), and the area under the curve from zero to the last quantifiable concentration (AUC(last)) for BP1001 were similar between Days 1 and 11. Tmax of BP1001 was 1.9 vs 2.3 h (day 1 vs 11); t1/2 was 5.2 vs 5.7 h; AUC(last) was 308 vs 275 h*ng/mL.

Response: Among 17 fully evaluable pts, 7 pts (41%) demonstrated bone marrow blast reduction, including 5 (29%) who achieved a CR (n=3), CRi (n=1), or morphologic leukemia free state (n=1). Two additional pts demonstrated a ≥50% reduction of bone marrow blasts (from 20% to 9% and from 71% to 8%), including 1 with hematologic improvement of the absolute neutrophil count. The median overall survival (OS) was 5.2 months (range, 0.6-15.2) for all patients. For evaluable patients, the median OS was 6.3 months (0.8-15.2 months). The CRs included: a 74-year old female who achieved CR after 2 cycles of therapy and then received 2 additional cycles followed by a matched-sibling allogeneic transplant. She remained in CR for 10 months before first relapse. A 73-year old female, with AML transformed from MDS, benefited from therapy despite refusal of blood products due to religious objections. Her hemoglobin declined to 4.0 g/dL during therapy but recovered to as high as 9.9 g/dL once in CR after 4 cycles. An 86-year old male achieved CR after 4 cycles of therapy and maintained CR for 3 months before relapse.

Conclusions: BP1001 has been safely administered to 25 pts with untreated AML, who were considered unsuitable for standard chemotherapy. Efficacy data are encouraging in a challenging population in which the majority of pts had secondary AML or adverse-risk AML, and compares favorably to the reported CR/CRi/CRp rate with LDAC of 7-13% (Heiblig, Mediterr J Hematol 2016; Kantarjian, J Clin Oncol 2012; Döhner, Blood 2014). A protocol amendment made to optimize BP1001 administration with LDAC and to add a decitabine combination arm is in place."

https://ash.confex.com/ash/2018/webprogram/Paper113693.html

These results confirm the delivery system works without any major side effects but to me the drug results are disappointing. Why would the FDA approve any drug that only demonstrates short term affects for less than 50% of the trial patients? I see no urgency for FDA approval.

IMO it appears that all PN is concerned about is the reverse split. Why would anyone buy this stock before the 1 to 20 reverse split? I expect that major shorting will occur once the R/S happens and we will move from $4.00 per share back to $.40 again!