Cervomed Inc. · NASDAQ:CRVO
Cervomed — Diffusion Pharmaceuticals — Technical Presentation (December 2019)
25 slides from Cervomed's technical presentation, Dec 10, 2019
Slide 1: TSC Treats GBM by Reducing Hypoxia
TSC Treats GBM by Reducing Hypoxia a Novel Approach John L. Gainer Chief Science Officer Diffusion Pharmaceuticals Inc. Charlottesville, Virginia
Slide 2: Forward looking statements
forward looking statements This presentation contains forward-looking statements within the meaning of U.S. securities laws that are intended to be covered by the safe hatbors created by those laws. These statements include, but may not be limited to, our operating and growth strategy, including our
Slide 3: The problem
e problem GBM is the most common and deadly type of primary malignant brain tumor If the patient cannot have an initial surgery, median survival rate is from 9-10 months. Because of such dire prognosis, these patients are frequently excluded from GBM clinical trials. Hypoxia has been implicated as a
Slide 4: The need
je need well oxygenated tumor cells are 2-3X more likely to be eliminated by radiation’ Little research has been done concerning hypoxia and chemotherapy, butit may be related to the effect of hypoxia on cell cycles. Is there a way to improve oxygenation in cancerous tumors? * Radiobiology for the R
Slide 5: Reducing hypoxia
reducing hypoxia Sn GBM - . TUMOR Brute force methods: INHALED O * increase concentration of O2 in inspired gas * increasing solubility of O2 in plasma by adding fluorocarbons or other chemicals PLASMA IN THE BLOOD STREAM but none of these have proven to extend survival
Slide 6: A solution from Chemistry: TSC
Asolution from Chemistry: T OTE ° sa GBM a . ) TUMOR INHALED . OXYGENATION TSC promotes the formation of additional hydrogen bonds among the water molecules of the blood plasma. PLASMA IN THE BLOOD This allows increased diffusional STREAM movement of small molecules like oxygen and glucose.
Slide 7: Oxygen versus Glucose
Oxygen versus Glucose % Increase in o Diffusivity 30-7 o ° 100 200 Concentration of TSC, micromole/iter Gainer, Expert Opinion, Trans-sodium crocetinate for treating hhypoxia/ischemia, 2008 Informa UK * Oxygen 5 Glucose Over-oxygenation does not occur because oxygen and glucose transport rates incre
Slide 8: A solution from Chemistry: TSC
Asolution from Chemistry: TS 30% increase of O2 paired with a 30% increase of glucose keeps metabolism “in balance”? Gainer, Expert Opinion, Trans-sodium crocetinate for treating hhypoxia/ischernia, 2008 Informa UK * INHALED THE LUNGS . GBM : TUMOR OXYGENATION WHEN GLUCOSE IS PRESENT
Slide 9: TSC
TSC “White Label" Drug: all safety studies in humans indicate that TSC has No known serious adverse effects. Easily administered by IV injection or IM injection. Oral administration in development phase.
Slide 10: TSC: Progress
TSC: Progress Phase 2 Clinical Trial TSC for Treatment of Acute Stroke Researchers at UCLA and UVA are cooperating on this trial involving the on-ambulance administration of TSC to 160 patients within 2 hours of the onset of stroke symptoms. Phase 3 Clinical Trial TSC for Inoperable GBM Patients Lea
Slide 11: TSC: Greater Implications
TSC: Greater Implications Hypoxia is the common denominator in over 23,000,000 patient cases per year HEMORRHAGIC ‘SHOCK 100,000 Battlefield Casualties (Office of Naval Research) Kauvar and Charles & Wade, The epidemiology and ‘modern management of traumatic hemorrhage: Crit Care. 2005; 9(Suppl 5):
Slide 12: Hypoxia is the common denominator in over 23,000,000 patient cases per year
Hypoxia is the common denominator in over 23,000,000 patient cases per year HEMORRHAGIC MULTIPLE ORGAN HEART ATTACK / RESPIRATORY SHOCK TRAUMA FAILURE STROKE ‘ONcoLocy CHE DISEASES 100,000 100,000 100,000 800,000 900,000 6,000,000 15,000,000 Centers for Disease Control and Prevention, https://iwwcde
Slide 13: TSC: Greater Implications
TSC: Greater Implications Poe Example: Stroke TSC supports immediate treatment of stroke symptoms without waiting for the in-clinic hemorrhagic v. ischemic determination.
Slide 14: GBM Clinical Trials by Diffusion Pharmaceuticals
GBM Clinical Trials by Diffusion Pharmaceuticals Phase 2 (100-202): Open-trial, 56 patients (all comers including biopsy-only). Surgery: if possible. Chemo-radiation Therapy: 0.25 mg/kg TSC IV on M,W,F 45- 60 minutes prior to 2 Gy radiation. Radiation given 5 days/week for 6 weeks. Temozolomide, 7 d
Slide 15: Phase 2 Trial (100-202) Results
Phase 2 Trial (100-202) Results (Published in J Neurosurg, 126:460-416, 2017) 2-Year Overall Survival: 36% versus 27% for SOC 3-Year Overall Survival: 22 % versus 16% for SOC However for Biopsy-Only Patients: 2-Year Overall Survival: 40% versus 10% for SOC
Slide 16: Results from Trial 100-202
Results from Trial 100-202 Comparison of Survival % Survival Ny 38 Complete Biopsy Resection Only Biopsy only patients treated with TSC had the same survival outcome as fully resected patients at 2 years.
Slide 17: Trial 100-202 Tumor Control
Trial 100-202 Tumor Control Size reduction in 37/41 tumor-bearing patients. Number of Patients 12 10 Tumor Reduction at 2 Years oN 8 Oo @ Up to 39% 40 -63% 64-93% 94-99% 100%
Slide 18: Phase 3 (100-206): Open-label, Randomized, Controlled
Phase 3 (100-206): Open-label, Randomized, Controlled, 236 patients, biopsy-only. Chemoradiation Therapy. 0.25 mg/kg TSC given as in Phase 2 trial. Adjunct Chemotherapy: Temozolomide, 150-200 mg/m2, given for days 1-5 of six 4-week cycles. TSC, 1.5 mg/kg, given on Days 1,3,5 one to two hours prior t
Slide 19: Principal Investigators
Principal Investigators Daniella Bota, M.D. — University of California Irvine Douglas Ciuba, M.D. — John B Amos Cancer Center Erin Dunbar, M.D. — Piedmont Physicians Neuro- Oncology Samuel Goldlust, M.D. — John Theurer Cancer Center Adilia Hormigo, M.D. —Icahn School of Medicine at Mount Sinai Micha
Slide 20: Why a Different Dose for Chemotherapy?
Why a Different Dose for Chemotherapy? One study in the literature suggested that oxygen and the chemo- therapeutic agent need to be administered at the exact same time to kill tumor cells. 0, wo! Pp Ea 50} —+—Highret TSC| 4} + Lowret TSC
Slide 21: Diffusion internal study verified that chemotherapy was far more efficient
Diffusion internal study verified that chemotherapy was far more efficient with high dose TSC when given 1-2 hours after IV injection --so escalation to high human dose (1.5 mg/kg) was selected for clinical study. Since this dose is higher than that used during radiation therapy, FDA suggested the f
Slide 22: Lead-in study results
LEAD-IN 19 patients enrolled in Lead-In Study. 11 patients completed the FDA- required protocol. Of those, 4 received a low dose (0. 25 or 0.5 mg/kg) of TSC while 7 received a high dose (1.0 or 1.5 mg/kg) of TSC. DSMB found no serious adverse events attributable to TSC for any TSC dose, and recommen
Slide 23: Comparison of Karnofsky Performance Scores (KPS)
Comparison of Karnofsky Performance Scores (KPS) at end of 18 weeks (FDA period) Median KPS Comparative KPS Values Radiation: Wks 1-6 400 Chemo: Wks 10-18 90 80 70 = 100-202 60 9100-206 50 40 30 - 0123 4 5 6 10 18 Weeks after Treatment Began
Slide 24: Currently: 6/7 high dose patients are still alive
Currently: 6/7 high dose patients are still alive. Fraction Surviving ecooo = Ga a8 on (Comparison of Treatments for Biopsy— Only Patients (Kaplan-Meier Survival Plot) Ne -_———— a = — 800-1325 100202-15 — 100206-7 0 5 0 68 0 2
Slide 25: Diffusion Seeking Partners
DIFFUSION SEEKING PARTNERS 5 N David Kalergis, CEO Bill Hornung, CFO
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