Mining protein-protein interactions for targeted cancer drug discovery
Higher-risk targets are often set aside when there is no good way to pursue them. The McInnes lab developed REPLACE so more of those targets can be reached.
The problem
Cancer is second only to heart disease in total mortality.
The numbers
1.6M+
New U.S. cancer diagnoses / year
Cancer remains second only to heart disease in total mortality.
~500K
U.S. cancer deaths / year
Highlights the persistent need for better-targeted therapies.
~80K
Prostate patients needing better options
Approximate cohort cited for improved treatment need.
$100K+
Cost per course of treatment
FDA approved drugs can cost over $100,000/course of treatment
Estimated Incidence and Mortality of Common Cancers
| Prostate / Breast | Lung | Colorectal | ||||
|---|---|---|---|---|---|---|
| Prostate / Breast Men | Prostate / Breast Women | Lung Men | Lung Women | Colorectal Men | Colorectal Women | |
| Incidence | 238,590(28%) | 232,340(29%) | 118,080(14%) | 110,110(14%) | 73,680(9%) | 69,140(9%) |
| Mortality | 29,720(10%) | 39,620(15%) | 87,260(28%) | 72,220(26%) | 26,300(9%) | 24,530(9%) |
U.S. estimates shown in the company overview for prostate, breast, lung, and colorectal cancers. Percentages are each figure’s share of all cancers for that sex.
Many chemotherapy agents have been in use for decades and very toxic drugs.
Drug targets
Potential drug targets in the human genome
SM targets
Biologics
“Undruggable”
Traditional pharma usually focuses on highly druggable targets, the low-hanging fruit.
Higher-risk targets are passed over when there is no good method.
The McInnes lab developed REPLACE to make more of those targets accessible to drug development.
Many companies are working on cancer drugs. The need is urgent, and 99% of candidates fail, so the field needs many approaches.
REPLACE is what sets PPI Pharmaceuticals apart.
The solution
A new era in cancer treatment
BRAF inhibitor — targeted therapeutic
Using targeted therapeutics, dramatic progress has been made in specific cancer types.
Others, including certain prostate, breast and pancreatic tumors, can often have survival times in months.
Continued research into molecular defects causing cancer and understanding cancer metastasis are key to future breakthroughs.
Resistance is a problem
Replace Technology
Abbapolin PK and Xenograft Activity
Table 3. PK properties for orally dosed abbapolins
- No overt signs of toxicity in dosed animals.
- Statistically significant reduction in tumor volume with 6369 and 6190.
Xenograft experiment performed by the lab of Marhj Pena, PhD. Data analysis assist from Max Chen, Ph.D.
Abbapolin Screening in the NCI-60 Panel
- Abbapolins 6157, 6171, and 6190 are active against cell lines in the NCI-60 cancer cell panel, including prostate, CNS, and colorectal lines (but not breast).
- COMPARE analysis strongly suggesting that they each possessed similar Mechanism of Action.
- COMPARE suggests a unique MofA among all compounds available and tested in the NCI-60.
| Tumor type | Cell line | 6157 | 6171 | 6190 |
|---|---|---|---|---|
| CNS Cancer | SF-268 | 5.73 | 7.63 | 10.00 |
| CNS Cancer (GB) | SF-295 | 1.69 | 0.67 | 1.99 |
| CNS Cancer (GBM) | SF-539 | 6.85 | 6.33 | 9.70 |
| CNS Cancer (GB) | SNB-19 | 2.53 | 1.29 | 2.99 |
| CNS Cancer (GB) | SNB-75 | 2.85 | 3.13 | 2.23 |
| CNS Cancer (GBM) | U251 | 3.44 | 2.33 | 3.30 |
| Colon Cancer | COLO 205 | 4.71 | 1.94 | 12.40 |
| Colon Cancer | HCT-116 | 3.72 | 3.06 | 6.90 |
| Colon Cancer | HCT-15 | 3.35 | 2.75 | 4.54 |
| Colon Cancer | KM12 | 1.14 | 1.10 | 3.11 |
| Colon Cancer | HT29 | 1.52 | 2.63 | 2.13 |
| Breast Cancer | MCF7 | 4.38 | 5.25 | 7.34 |
| Breast Cancer | MDA-MB-231 | 15.00 | 22.40 | 16.90 |
| Breast Cancer | HS 578T | 18.8 | 23.1 | 20.5 |
| Breast Cancer | BT-549 | 18.50 | 6.85 | 20.00 |
| Breast Cancer | T-47D | 18.8 | 15.6 | 14.4 |
| Breast Cancer | MDA-MB-468 | 3.44 | 3.82 | 5.25 |