Ilike to think of the DEP (dendrimer-enhanced product) version of an existingdrug as a ‘Super’ version of the original drug because of the superior (enhanced)characteristics conferred by being attached to the carrier dendrimer molecule.
Pleaseread my prior post ‘The amazing value of DEP technology’, if you want to learn moreabout the science of DEP and how it can: provide targeted delivery; improve theeffectiveness; reduce toxicity and side effects; and improve the pharmacologicalproperties of a drug.
https://hotcopper.com.au/threads/the-great-value-of-the-dep-platform-technology.6015665/
Currentlywe have three drugs in phase 2 clinical trials. I like to think of them as: ‘SUPERDOCETAXEL, SUPER CABAZITAXEL, and SUPER IRINOTECAN’. (DEP Docetaxel, DEPCabazitaxel and DEP Irinotecan).
Standard(un-improved) Docetaxel, cabazitaxel and irinotecan are establishedchemotherapy drugs, in common usage, so their clinical usefulness is alreadyestablished. So SUPER versions of each of them (more effective, less toxic,less side effects) I expect would be quickly embraced by researchers (furtherindependent clinical trials/combinations) and treating oncologists, due tofamiliarity with the original drugs. Demonstration of greater effectiveness andless toxicity would encourage oncologists to try the ‘SUPER’ (DEP) versions ina wider range of patients (including sicker patients) and a wider range ofcancers, increasing their overall usage compared with the original drugs. Forthese reasons, I believe the DEP versions will represent a MUCH LARGER MARKETthan the original drugs.
Tohave an idea of possible market size, ‘Plain’, ‘unimproved’ Docetaxel, in 2010,just before it came off patent, earnt over 3 million USD in revenue. I imaginethat DEP Docetaxel should earn a great deal more than that if it is confirmedto be more effective, safer and have less side effects, as well as being usefulin a wider range of cancers and a wider range of patients (sickerpatients).
Inthe case of irinotecan, its extreme toxicity significantly limits it use. DEPIrinotecan is shaping up to be far less toxic, with less side effects (seebelow) so I believe it is likely to be much, much more widely used than theoriginal drug. Again, representing a much larger market and earnings than theoriginal ‘unimproved’ drug.
So,how are our ‘SUPER DRUGS’ going in phase 2 trials?
Istheir use in the clinic proving to as impressive as the super-impressive sciencebehind them suggests they should be?
Arethey proving to be as impressive in clinical trials as they were clearlydemonstrated to be in super-impressive pre-clinical data?
Ihave gone through investor updates, AGM addresses and ASX announcements andpicked the eyes out of the announcements to summarise and condense what Starpharmahas released about results of the phase 2 trials, concentrating on patient casestudies. It was obvious that some patients have been presented more than onceduring their journey. In these cases I have left out the earlier references andonly included the most recent update. I have copied and pasted from theannouncements and then done very minimal editing (such as highlighting).
Thisis only a tiny snapshot of what is going on in the trials. I think thesereleased case study results TRULY ARE SUPER (actually SPECTACULAR) consideringthey are in heavily pre-treated patients (in most cases they have exhausted theiroptions with currently available treatments and would be sick patients withweak immune systems) and some of these patients have the hardest-to-treat typesof cancers, with very poor prognosis / life expectancy.
Weshould all finally find out just how super these drugs really are later thisyear, when the full phase 2 trial results are finally released. I believe theywill all be released close together, or at the same time, as a deliberatestrategy by Starpharma to clearly demonstrate the value of DEP as a PLATFORMTECHNOLOGY which is incredibly valuable because it can be applied to many,many existing drugs and to drugs under development. Starpharma will then beable to extract the maximum monetary value for selling or licencing individualDEP drugs, or the DEP technology to large pharmaceutical companies. I believethe approaches by large pharmaceutical companies will be fast, furious andcompetitive, with big dollars involved, when they get to see the final data. Ibelieve these large companies will strongly desire this technology and beprepared to pay big dollars for it. I expect these companies to also show greatongoing interest in partnering with Starpharma to use DEP for improving otherold drugs, and for developing new drugs.
Ofcourse, a takeover bidding war is also a strong possibility.
Also,I offer my speculation/opinion as why these phase 2 trials have taken so long, which has concerned someshareholders. The first reason may be a strategy to release the results of the3 trials together, or close together, to gain maximum value, as discussed above. We have seen rapid recruitment in the irinotecan trial with slower recruitment in the others, over the last year. The second reason, I suspect, is because the patients are doing so well, it istaking a very long time to gather endpoint statistics such as progression-freesurvival (PFS) and median overall survival (OS). In other words, when youare running a cancer trial, the longer it takes to get PFS and OS outcomes, themore likely the results are going to be good!
Otherreasons for the trials taking so long could be explorationof use of agents in different cancer types (expanding indications) to add further value (while awaiting PFS and OS figures for people dosed earlier in the trials);and no-doubt there would have been some delays in recruitment due to COVID 19.
Thisis my opinion. Not investment advice. Please have a read of my condensedsummary below and make up your own mind. What do you think?
CONDENSED MATERIAL FROM STARPHARMA RELEASES (highlighting done by me):
MAY 20 UPDATE:
DEP® docetaxel:
Thephase 2 DEP® docetaxel trial is progressing well, with further observations ofencouraging efficacy signals in very heavily pre-treated patients. Theseinclude prolonged stable disease and substantial target tumourshrinkage in patients with cancers including lung, prostate, pancreatic,gastric and oesophageal cancer.
DEP® cabazitaxel:
Inthe DEP® cabazitaxel phase 2 trial - encouraging efficacy signals have beenobserved, including prolonged stable disease (>47 weeks),significant target tumour shrinkage and substantial tumour markerreductions (e.g. PSA), in cancers including prostate, ovarian, lung,gastroesophageal and others.
INVESTORPRESENTATION SEP 20:
46 year old man with stageIV lung cancer (NSCLC):
• Genetic profile limited treatment options (he didn't qualify for 1st line immunotherapy)
• Pre-treated: Cancer hadprogressed after 7 cycles platinum-based chemo + immunotherapy & aninvestigational enzyme inhibitor
• Received x2 cycles of DEP® docetaxel+ nintedanib
• Reduction in size of tumour lesionsof up to 45%
• Stable disease > 9 weeks
• Improvement in tumour-related pain
70 year old man with stageIII prostate cancer:
• Heavily pre-treated: cancerprogressed on 4 other anti-cancer therapies
• Was unable to tolerate docetaxel dueto toxicity (neutropenia)
• Received 15 cycles of DEP®cabazitaxel with no neutropenia
• Response to DEP® cabazitaxel beganat 40% of the typical dose of plain cabazitaxel.
• Prolonged stable disease >47weeks
• PSA stabilised following a 79%decrease
OCT 20 SHAREHOLDER UPDATE:
Patientbiopsies demonstrate tumour targeting of DEP® docetaxel During the phase 2 DEP®docetaxel trial, multiple patient tumour biopsies have demonstrated that thesame tumour targeting observed with DEP® in animal studies has also beenreplicated in patients treated with DEP® docetaxel, delivering substantiallyhigher levels of drug than in blood.
This accumulation of DEP® drug in tumour tissue is animportant benefit of DEP® which has been demonstrated in multiple preclinicalstudies.
72 year old woman withextensive intrahepatic cholangiocarcinoma:
Anoften-fatal cancer that affects the bile ducts Cholangiocarcinoma is a rare butaggressive form of cancer. The 5-year survival rate for intrahepaticcholangiocarcinoma is very low (8%).
•Heavily pre-treated Patient was having progressed following 8 cycles ofprior anti-cancer therapy
•Patient received 4 cycles of DEP® docetaxel and achieved >16 weeks stabledisease
•A tumour biopsy following dosing with DEP® docetaxel and showed 63-fold moreDEP® docetaxel in the tumour tissue than in blood (i.e. a tumour to bloodratio of ~63x)
NOV 20 CEOADDRESS TO AGM:
66-year-old man: stage IVoesophageal cancer with liver metastases:
• Heavily pre-treated patienthad progressive disease after radiotherapy and 9 cycles of two differenttreatment regimens.
• Reduction in size of tumour lesionsof up to 48%; maintained for >16 weeks
65-year-old man withlate-stage (metastatic) gastro-oesophageal cancer:
• Heavily pre-treated patientwith >15 cycles & three different kinds of anti-cancer treatment andcancer progressed
• Patient received 6 cycles of DEP®cabazitaxel and achieved a 50% reduction in total tumour size maintained for>27 weeks
60-year-old woman withadvanced (metastatic) ovarian cancer:
• Heavily pre-treated; cancerprogressed on 3 other anticancer therapies including paclitaxel (anothertaxane); Previously had 14 cycles of treatment and multiple surgeries
• Patient received 6 cycles of DEP®cabazitaxel - response seen after 3 cycles of treatment with overall response:
• 40% reduction in total tumour burden
• 50% reduction in biomarkers
60-year old male with stageIV oesophageal adenocarcinoma (metastatic):
• Heavily pre-treated previouslywith 6 cycles with 3 different agents
• Response to DEP® irinotecan seenafter 3 cycles of treatment; 4 cycles of DEP® irinotecan treatment to date
• Stable disease >9 weeks; 71%reduction in tumour biomarkers (CA 19-9); well tolerated, minimal side effects
45-year old woman with stageIV breast cancer with extensive liver metastases:
• Extensive metastases including inthe liver
• Very heavily pre-treated with>100 cycles of 11 different treatment regimens
• Response to DEP® irinotecan seenafter 3 cycles of treatment
• 20 cycles of DEP® irinotecantreatment to date; well tolerated
• Prolonged stable disease >54weeks; 21% reduction in target tumours DEP® irinotecan case studies. CT Scanshowing 30% reduction in size of liver metastasis
QTRLY JAN 21
DEP® irinotecanphase 2 trial continues toprogress well. Encouraging efficacy signals have been observed for a number oftumour types, including breast, colorectal, ovarian, pancreatic, lung andoesophageal cancer. Efficacy signals include tumour shrinkage and stabledisease including 72 weeks’ stable disease in a breastcancer patient (*likely same 45 year-old patient as presented at AGM addressabove).
These efficacysignals are particularly encouraging given the heavy pre-treatment in trialpatients, who average ~30 dosing cycles of anti-cancer therapy and an averageof four different types of treatment before entering the DEP® irinotecan trial.
DEP® docetaxelclinical trials continue toprogress well, with encouraging efficacy signals observed, including prolongedstable disease and tumour shrinkage in patients with pancreatic, oesophagealand gastric cancer. Patients treated with DEP® docetaxel continue to experienceless neutropenia than is usually associated with the standard version ofdocetaxel (Taxotere®) and have not required pre-treatment with cortisone.
DEP® cabazitaxelphase 2 trial continues toprogress well, with encouraging efficacy signals observed, including stabledisease, significant target tumour shrinkage and substantial tumour markerreductions (e.g. PSA), in cancers including prostate, ovarian, lung,gastro-oesophageal, head and neck and other cancers. Patients treated with DEP®cabazitaxel continue to experience less neutropenia than is usuallyassociated with the standard version of cabazitaxel (Jevtana®) and have notrequired pre-treatment with cortisone.
QTRLY APRIL 2021
DEP® irinotecanphase 2 trial continues to progress well, with morethan 40 patients now recruited. Encouraging efficacy signals observed includeprolonged stable disease, impressive tumour shrinkage and reductions in tumourmarker levels for a number of tumour types, including breast, colorectal,ovarian, pancreatic, lung and oesophageal cancer.
A patient with heavily pre-treatedmetastatic ovarian cancer (*likely update on same 60year old patient as presented at AGM address above) experienced a 98%reduction of tumour marker (CA-125) following 7 cycles of DEP® irinotecan,and follow up scans showed a complete disappearance of her ovariantarget tumour.
DEP® docetaxelclinical trials continue to progress well,with more than 40 patients now recruited and encouraging efficacy signalsobserved, including prolonged stable disease and tumour shrinkage in patientswith pancreatic, oesophageal, and gastric cancer. These impressive tumourresponses include stable disease for up to 40 weeks andsignificant tumour shrinkage in a heavily pre-treated oesophageal cancerpatient, maintained for more than 28 weeks (*likelyupdate on same 60 year-old patient as presented at AGM address above).
In addition to the monotherapy of DEP® docetaxel, Starpharmais also recruiting into a study combining DEP® docetaxel withgemcitabine. This study follows compelling data for this combinationin pre-clinical human pancreatic cancer models.
DEP® cabazitaxelphase 2 trial continues to progresswell, withmore than 35 patients now recruited. Encouraging efficacy signals have beenobserved, including stable disease, significant target tumour shrinkage andsubstantial tumour marker reductions (e.g., PSA), in cancers includingprostate, ovarian, lung, gastro-oesophageal, head and neck and other cancers.These impressive tumour responses include significant tumour shrinkageincluding in prostate and ovarian cancer, in patients who have failed multipleother lines of cancer treatment.
(20min delay)