Steve King's UBS Pharma. Conference Talk 5-25-04
Went back over the replay, and cleaned up my earlier post on RB - these notes are pretty accurate now...
http://event.streamx.us/event/default.asp?event=ubs20040524
PPHM: 20 emps Avid: 60 emps $14.9mm a/o 4-30-04 Burn: $1.0mm/mo.
15.8% Instit. Shelf: 8.7mm shares still avail.
PPHM’s main Prod Dev. Classes:
1) Vascular Biology Pgm. (cancer, expanding into angiogenesis&vasculature-diseases)
2) TNT – targets dead core of solid tumors (Cotara Ph3-Brain, and Stanford Ph.1)
Vascular Biology Pgm: based on targeting blood vessels, primarily tumor vessels, but we are looking at other disease types.
Anti-PS (3G4/Tarvacin) for Cancer:
Our lead agent that targets tumor vascular: Anti-PS (trade name Tarvacin). Our lead compound is a Chimeric mab based on a murine antibody named 3G4 binds to phospholipids, primarily phosphatidylserine [PS]. 3G4 tests in animals in every tumor type we’ve tried so far results in moderate-to-strong localization to tumor blood vessels. This includes Hodgins, non-small-cell lung, colon, melanoma, breast, & pancreatic cancers. No localization to normal tissues. Following therapy with 3G4 (parent antibody of Tarvacin), we see a massive infiltration of immune cells which are attacking the tumor. This attack is mediated thru the vascular - macrophages very much aligning the blood vessels as they enter the tumor tissue. Therapy experiments we’ve seem very good anti-tumor effects. Ex: human breast cancer grown in mammary tissue inside a murine model, 3G4 has significant antitumor effect. When 3G4 combined with the chemo Docetaxol, tests show 3G4 has the real potential to be an additive therapy with std. chemo. Animal tests showed “virtually no toxic side effects at all” with 3G4, vs. some toxic side effects with Docetaxol. Also, not additive toxicity when the 2 agents are given in combo. 3G4 also stops metastases to lungs & liver of experimental animals.
Summary: Tarvacin+3G4 therapy has shown significant anti-tumor effects in a number of tumor models, incl. breast cancer, fibrosarcoma [tumor of the deep structures of the skin, most often affecting bone], Hodgins disease, prostate cancer. 3G4 is extremely well tolerated, with no physical signs of toxicity or chgs. in blood counts, bone marrow, etc. . Only when dosage approaches 100 times theraputic dose do you see moderate toxicity.
Tarvacin/3G4 Dev. Plan: animal proof-of-principle done, prod. cell lines done, SAB established, safety studies on various disease models done , toxicology screen in Primates done, CMGF Mfg. ready, preclinical toxicology studies in progress, leading to IND before end of 2004.
Anti-PS for Other Diseases:
Also evaluating Anti-PS for Viruses: not based on targeting vascular, but rather the fact viral infected cells expose amino-phospholipids on their surfaces. Proceeding under $1.68mm Natl. Insti. of Allergy & Infectious Diseases grant, along with UT-SW.
Also evaluating Anti-PS for the delivery of various therapeutic agents to tumor vasculature, incl. lyposomes, toxins, cytokines, as well as use as imaging platform.
Also evaluating Anti-PS for Ocular diseases (angiogenesis-dependent diseases). Studies to begin shortly in collaboration with the Foundation for Fighting Blindness.
Now working with Affitech & Aeres to develop a fully-human (or humanized equivalents) versions of 3G4. Could be 2nd generation Tarvacin or for use as primary therapeutics for viral & ocular diseases.
VTAs cause blood stoppage to the tumors, killing them. Can work as therapy or imaging agents. Validated in a number of preclinical models, with wide variety of targets and effectors. Potentially the next gen. of therapeutics.
PPHM VTA PATENTS: > 190, covering delivering therapy agents, coagulation proteins, and imaging agents. Very broad claims, covering the concept of delivering any therapeutic agent to tumor vascular.
Internal Dev. activities: Anti-PS and VEGF
Licensing opportunities: Vegf/SUPG, Imaging/ScheringAG, more expected
Also developing agents that block tumor angiogenesis – stops new blood vessels
2C3 Anti-angiogenesis Antibody Program:
2C3: a murine antibody that binds to specific Vefg regions involved in Rec.2, not Rec. 1 which involves normal functions.
2C3 animal tests: breast, lung, fibrosarcoma, Hodgins disease, colon, and ovarian
2C3 preclinical done, collaborating to human or humanized 2C3, now identifying candidate to move FWD to human clinic
VEA: TNT delivers portion of IL2 (vascular leak syndrome) – pretreatment for existing therapies, like chemo. Increases update of agents into the tumor. Has broad application across diff. tumor types.
Preclinical construct identified for VEA, fully human antibody against DNA histone complex, fused to PEP (a portion of IL2). Ex: VEA & Taxol – significant incr. in efficacy of Taxol.
VEA status: animal proof done, have identified the clinical candidate, now generating prod. cell for cGMP, next: tox studies & IND filing
TNT: deliver therapeutic drugs that bind to necrotic core – broad spectrum agent.
Have completed imaging studies for: brain, lung, colon, pancreatic, liver, prostate cancers
Cotara is chimeric mab loaded with I131.
Cotara Brain: Phase I/II done, FDA has approved Prod. Reg.Trial, which we will begin with a partner for product approval in recurrent GBM (Orphan status in USA & Europe, Fast Track). Cotara injected into tumor can deliver several-fold higher radiation than with external beam.
Also, have completed a study in Mexico in conjunction with large pharma to eval. to localize for brain, prostate, and pancreatic cancers.
Also, ongoing Ph.1 study at Stanford to eval. safety and also localization to colorectal cancer.
Also, a TNT agent similar to USA version received SDFA approval in China for Lung cancer.
Promising result of brain program: 25% survived > 1 year. Some > 3 years. Brain cancer is very deadly with median survival of 6 mos.
Data from Medipharm: 12 centers, 107 patients, 4 comp, 33 partial – total resp. rate 34%, in very diff. to treat Adv. Lung cancer.
Plans: expand TNT/Cotara program: resume brain, will finish colorectal trial at Stanford, then expand to other cancers: lung (China) and hepatic (earlier promising results).
AVID - cGMP Mfg. facility spun out Jan2002 – continues to grow cust. base, while providing Peregrine with $2+mm of [internal] services per year, which will increase.
Goals: final stability thru licensing, strategic partnerships potential with Avid, equity financing/shelf.
Product Dev. Goals for 2004:
1. Initiate Phase 1 trial for Tarvacin
2. Begin product registration brain cancer trial with a corporate or funding partner
3. Complete Phase I colorectal carcinoma clinical trial at Stanford
4. Expand the potential indications for Cotara by initiating a Phase II study
5. Identify clinic candidates that we can move into clinical trials for both VEA and AntiVEGF
6. Enter into strategic licensing or product dev. agreements around our VTA technology where we have our broad intellectual property.