Aphton is expected to announce PIII results for Insegia for gastric cancer by year end, which is obviously very soon. The company has a reputation for spinning results, which is easier for PII. This was in fact discussed by many biofreaks in great detail earlier this year on the Valuation thread:
Message 19772730
Consensus seemed to be that the PR was indeed a bit spun, but that the drug probably was having some effect . . .
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FWIW, full results were also presented at ASCO; here's the abstract, which adds a couple of minor details:
>>Final data of the multicenter phase II study of cisplatin (CDDP) and 5-fluorouracil (5-FU) in combination with G17DT Immunogen in chemonaive patients with locally recurrent or metastatic gastric and gastroesophageal cancer.
Abstract No: 4048
Citation: Journal of Clinical Oncology, 2004 ASCO Annual Meeting Proceedings (Post-Meeting Edition). Vol 22, No 14S (July 15 Supplement), 2004: 4048
Author(s): D. Michaeli, J. R. Hecht, M. Oortgiesen, A. Eduljee, W. D. Perkins, J. A. Ajani; Aphton Corporation, Woodland, CA; UCLA School of Medicin, Los Angeles, CA; Cato Research, Durham, NC; MD Anderson Cancer Center, Houston, TX
Abstract: Background: G17DT is an immunogen designed to raise antibodies to the growth factor gastrin 17 (G17). The purpose of the study was to determine the safety and efficacy of G17DT in combination with CDDP and 5-FU. Interim data indicated a correlation between survival and anti-G17 immune response, which was further explored in analyses of the final data. Methods: Main eligibility criteria for the open label study were: metastatic or locally recurrent gastric/gastroesophageal cancer; measurable disease; chemotherapy naive; intact organ function; KPS=70. Patients received G17DT (500 µg, im) treatments at wks 2, 6, 10 and 26; CDDP 100 mg/m2 d1; continuous infusion 5-FU 1000 mg/m2 /d d1-5 q28 days. Endpoints: tumor response (per RECIST), survival, immune response and safety. Results: A total of 102 patients were enrolled. The best overall tumor response was 1 CR (1%), 39 PR (49%), 25 SD (32%) and 14 PD (18%). One patient, with PR, converted to CR after additional G17DT treatment in an extension protocol. Overall median survival was 8.7 months. The immune response occurred in 63% patients with anti-G17 titer = 1 ELISA unit for 2 consecutive wks; 75% with at least 1 titer = 1. Toxicity was consistent with CDDP+5-FU except for 3 NCI-CTC Grade-3 injection site reactions attributed to G17DT. Multivariate analysis showed the immune response as a predictor of tumor response and survival (Log rank: p=0.032 and p<0.001, respectively). Median survival was 10 months for anti-G17 responders and 2.3 months for non-responders. With the exception of performance status, no baseline parameters such as sex, age, race, location of metastases or organ systems involved with metastasis(es) significantly correlated with the anti-G17 response. After adjustment for KPS, the correlation between the anti-G17 response and survival remained statistically significant (p<0.001). Conclusion: The G17DT immune response predicts response and survival in untreated, advanced gastric cancer patients, offering promising prospects for an improved anti-cancer treatment regimen.<<
More recently, the chances of this trial were given a rough thumbs up or down treatment by Peter and rkrw -- except that they have their thumbs only halfway up.
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Aphton is optionable, and it has not run up in anticipation and remains closer to lows than highs. This indicates that the market doesn't expect much. This combo seemed to work a bit better than with irinotecan, for what that's worth:
>>A multicenter phase II study of irinotecan in combination with G17DT immunogen in subjects with metastatic colorectal adenocarcinoma (CRC) refractory to previous irinotecan-based chemotherapy.
Abstract No: 3573
Citation: Journal of Clinical Oncology, 2004 ASCO Annual Meeting Proceedings (Post-Meeting Edition). Vol 22, No 14S (July 15 Supplement), 2004: 3573
Author(s): C. M. Rocha Lima, R. Buck, K. Meyer, I. Mitrica, W. Perkins, D. Michaeli; University of Miami & Sylvester Cancer Center, Miami, FL; Cato Research Ltd, Durham, NC; Aphton Corporation, Miami, FL
Abstract: Background: G17DT is a novel immunogen that raises antibodies to the growth factor gastrin-17 (G17). The purpose of this study was to determine the safety and efficacy of G17DT in combination with irinotecan in metastatic CRC subjects refractory to previous treatment with irinotecan-based chemotherapy and to correlate this with anti-G17 immune response. Methods: The study was an open-label, multinational, phase II trial in subjects with intact organ function, KPS>70, and measurable disease. Subjects received irinotecan 125 mg/m2/90 min wk 5-8 q42 days. 500 µg G17DT was administered I.M. wk 1, 5, 9 with a booster at wk 26. Results: 158 subjects received G17DT, with 98 evaluable for tumor response. Best overall response was: CR (0%), 3 PR (3%), 32 SD (33%), and 63 PD (64%). Median survival was 219 days. 103 (69%) of subjects evaluable for antibody titers were immune responders (i.e., had at least one anti-G17 antibody titer >1 ELISA unit). Non-whites (95%) were more likely to be immune responders than whites (64%). Mean peak titer was 47.2 +/- 133.4; median peak titer was 3.7 U. Cox regression analysis showed anti-G17 immune response to be a predictor of survival (median survival in immune responders was 273 days) which remained statistically significant after adjusting for KPS (p <0.0001). There was no difference in sex, age, location of metastasis(es), and number of organ systems with metastasis(es) between the populations of anti-G17 responders and non-responders (when comparing baseline characteristics). Toxicity was consistent with irinotecan (diarrhea, nausea, anemia, vomiting, fatigue, anorexia, and neutropenia) except for injection site reactions (pain, induration, erythema, edema, and two abscesses) attributed to G17DT. Conclusion: The combination of G17DT with irinotecan results in an acceptable anti-G17 immune response, which correlated with promising survival in CRC subjects previously treated with irinotecan. Additional studies with G17DT in combination with chemotherapy for CRC are warranted.<<
Also presented at ASCO was this paper regarding the importance of being an antiG-17 immune responder. If one could easily determine that at diagnosis (there ain't much time with gastric cancer), it would help target the folks most likely to benefit. That doesn't really have a major investment implication at this time:
>>Immune response to Gastrin-17 is an independent covariate in determination of survival in colorectal, gastric and pancreatic cancers.
Abstract No: 4073
Citation: Journal of Clinical Oncology, 2004 ASCO Annual Meeting Proceedings (Post-Meeting Edition). Vol 22, No 14S (July 15 Supplement), 2004: 4073
Author(s): P. Broome, R. D. Buck, D. Michaeli; Aphton Corporation, Hertfordshire, United Kingdom; Cato Research, Durham, NC; Aphton Corporation, Woodland, CA
Abstract: Background: Many gastrointestinal (GI) cancers express the gastrin CCK2 receptor and are sensitive to the mitogenic effects of autocrine/endocrine Gastrin-17 (G17). The immunogen G17DT elicits antibodies that neutralize G17, thereby blocking its proliferative activity. We analyzed the data from three clinical trials in three different GI cancers to determine the extent of dependence of the effect of the G17DT antibody response on survival from general health status. Methods: A G17 immune responder was defined as a subject with an anti-G17 titer > 1 ELISA unit. The relationships of demographics, tumor stage at onset, number and location of metastases, baseline Karnofsky performance status (KPS) and laboratory values to immune response were examined in each study; their joint relationships with immune response on survival was analyzed using Cox regression analysis. Results: In 158 metastatic colorectal cancer patients who had previously failed chemotherapy, median survival (MS) was 227 days; MS of G17 responders was 249 days vs. 119 days for non-responders (p<0.001, log-rank). For 102 advanced gastric cancer patients on chemo-immunotherapy, MS was 265 days; for G17 responders, 303 days vs. 70 days for non-responders (p<0.001, log-rank). In a placebo-controlled trial in 152 stage II-IV pancreatic cancer patients, MS was 111 days; MS of G17 responders was 176 days, of non-responders 63 days and of the placebo group 83 days (p=0.028, log-rank). With the exception of race (for colorectal cancer) and KPS, no parameter significantly affected the antibody response to G17. After adjustment for KPS (from 70-100%) the anti-G17 response remained a significant determining factor for survival in a Cox proportional hazards model (p<0.001) in all 3 trials. Conclusions: Subjects with advanced colorectal, gastric or pancreatic cancers, who generated antibodies to G17 following immunization with G17DT, had a significantly prolonged survival compared to those who did not. This effect was independent of other covariates analyzed.<<
In summary, one might take a bit of gambling money and buy a few options. Very high risk, very high reward. Somewhat equivocal results, properly spun, might give a few extra minutes to get out when the PR gets on the wires. However, the implied volatilities of the January calls at the strikes of 2.5 and 5 are both in the 200%. Pretty darn high, but with the 2.5 having "only" .6 in time premium, the stock would "only" have to move up in excess of 20% to ensure a profit. I think good results would more than do that. But again, odds of success are probably 50-50 or less.
Given the implied volatilities, perhaps simply buying the shares is a better alternative. Perhaps even a covered write or put sale. I'm starting to lean towards this last idea; there is a bit of pipeline. According to Yahoo! they have 1.31/share in cash. I'm guessing downside to about $1.5 on utter failure, and invite guesses from others.
Perspectives from other biofreaks welcome. In particular, I'd like to see folks hazard a guess on odds of success, and what strategy they favor.
Cheers, Tuck |
