Chris Heminway, Exec-Chair at Time To ACT, explains why now is the right time for the Group to IPO. Watch the video here.
Indeed Potnak, BBI-355 & the Brain penetrant version BBI-098 which they regard as 2nd generation.
These posts and musings will no doubt lead to the oft repeated "did the patents get handed back to the CPF/Sareum" questions, or "does this mean they patented SRA737 to prevent others using it..." and "Parker said this, but meant that about the asset".
I guess its all supposition until a trial or update breaks cover.
Fun and games as ever.
ATB
1.
Myrobalan Therapeutics Completes Series A Financing of $24 Million to Develop Potentially First-in-Class CNS Therapeutics with Restorative Potential - They have an allosteric TYK2i...
https://finance.yahoo.com/news/myrobalan-therapeutics-completes-series-financing-114500871.html
2. J.P. Morgan Day Three: Biogen Still Shopping For Deals, Sanofi Explains Its View On Oncology
10 Jan 2024 - Takeda To Take TYK2 Inhibitor Into IBD At High Dose
https://scrip.citeline.com/SC149610/JP-Morgan-Day-Three-Biogen-Still-Shopping-For-Deals-Sanofi-Explains-Its-View-On-Oncology
3. Science heavy, but a good read: New and Emerging Biological and Oral/Topical Small-Molecule Treatments for Psoriasis:
https://www.preprints.org/manuscript/202401.0800/v1
direct .pdf: https://www.preprints.org/manuscript/202401.0800/v1/download
4. https://www.dermatologytimes.com/view/hello-2024-what-surprises-are-in-store-for-dermatology-this-year-
5. Identification and validation of the association of Janus kinase 2 mutations with the response to immune checkpoint inhibitor therapy:
https://link.springer.com/article/10.1007/s00011-023-01833-w#Sec21
ATB
Good morning HBD,
An excellent post, I recall the discussions here way back regarding Christian Hassiq and indeed Triparna Sen being named on an SRA737 patent, and the move to Boundless Bio for Hassig; it certainly piqued some interest at the time.
As you can probably imagine, I have several pages bookmarked regarding Hassig, his patents and movements as he is IMO the most obvious potential suitor to take SRA737 forwards having seen the potential whilst at Sierra Oncology.
These things take time, but its certainly interesting to dig and delve, looking for snippets and leads. One must keep the mind sharp and trained as much as the body - (I much prefer this to crosswords & sudoku's so its a win!)
As a side note, and as you are clearly aware, looking at patents can really provide an insight into the science and potential direction for companies - doing so has provided very good early "ins" when investing in the past - sew up the intellectual property and protect the potential assets early and a company is already doing more than many of their competitors. Something I feel Sareum has been very good at! "News flow" & creating a buzz, not so much!
Thanks again for your excellent posts
ATVB
Happy new year one and all !!
Something or nothing, but as HBD mentioned, newly published Patents are a great area in which to dig for info.
Could our CHK1i have be taken on by Numedii Inc… https://numedii.com/
"About NuMedii, Inc.
NuMedii, Inc., discovers effective new drugs by translating its predictive data intelligence technology into therapies with a higher probability of therapeutic success. The Company's exclusive Big Data technology, originally developed at Stanford University, utilizes large amounts of scientific data together with proprietary biological network-based algorithms to discover drug-disease connections and biomarkers that are predictive of efficacy. NuMedii translates these predictions into novel de-risked drug candidates and partners with pharmaceutical companies for development and commercialization. Headquartered in Palo Alto, California, NuMedii's investors include Claremont Creek Ventures and Lightspeed Venture Partners."
Patent flagged up as follows:
“Method for treating idiopathic pulmonary fibrosis
Abstract
Provided is a method of treating idiopathic pulmonary fibrosis (IPF) using an agent that reduces or eliminates the kinase activity of checkpoint kinase 1 (Chk1).”
https://patents.google.com/patent/WO2020154608A1/
full .pdf: https://patentimages.storage.googleapis.com/1a/77/26/ef2bab65850e7b/WO2020154608A1.pdf
As ever, every CHK1i under-the-sun is to be mentioned….
But delving into the document its clear extensive testing has been carried out using various CHK1i molecules.
SAR020106, CCT244747, CCT245737 all mentioned, but just how many other molecules are/were available for partnering…?
Food for thought and as tenuous & flimsy as you like, but good fun for the old grey matter whilst we await SDC1801 news.
On social media/their own website etc. Numedii haven’t been that active, but clearly they saw value in CHK1i as applying for patents isn’t a cheap endeavour!
They also have a history of repurposing later-stage assets, and passing them on to a bigger fish....
ATB
Some here might like this:
Cost in the United States of FDA-approved small molecule protein kinase inhibitors used in the treatment of neoplastic and non-neoplastic diseases:
https://www.sciencedirect.com/science/article/pii/S1043661823003924
Table 6. FDA-approved small molecule JAK family blockers.
Drug Target Disease Cost/30 days Cost/year Generic Approved
Neoplastic Diseases
Fedratinib JAK2 Myelofibrosis $25,000 $300,000 No 2019
Momelotinib JAK2 Myelofibrosis patients with anemia $25,000 $300,000 No 2023
Pacritinib JAK2 Myelofibrosis $12,000 $144,000 No 2022
Ruxolitinib JAK1/2/3, Tyk2 Myelofibrosis, polycythemia vera, atopic dermatitis (applied topically) $18,000 $216,000 No 2011
Non-neoplastic Diseases
Abrocitinib JAK1 Atopic dermatitis $5600 $67,200 No 2022
Baricitinib JAK2/1 Rheumatoid arthritis $2500 $30,000 Yes 2018
Ritlecitinib JAK3 Alopecia areata $4200 $50,400 No 2023
Tofacitinib JAK3 Rheumatoid arthritis, psoriatic arthritis, ulcerative colitis $5000 $60,000 Yes 2012
Upadacitinib JAK1 Rheumatoid arthritis, psoriatic arthritis, atopic dermatitis $6000 $72,000 No 2019
These treatments are far from cheap!
Hopefully the table above is readable ! ;)
ATB
1. Bibliometric analysis and description of research trends on T cells in psoriasis over the past two decades (2003–2022):
https://www.sciencedirect.com/science/article/pii/S240584402310750X#sec5
"Research has established the efficacy and long-term safety of targeted inhibition of T cell-related targets. Deucravacitinib, a psoriasis treatment drug targeting TYK2 as an allosteric inhibitor, has attracted significant attention and raised high expectations."
2. Effectiveness of switching from baricitinib 4 mg to upadacitinib 30 mg in patients with moderate-to-severe atopic dermatitis: a real-world clinical practice in Japan:
https://www.tandfonline.com/doi/full/10.1080/09546634.2023.2276043
"Total EASI, EASI at each anatomical site, EASI of each clinical sign, and PP-NRS were markedly reduced at weeks 4 or 12 compared to week 0. Achievement rates of more than 75% or 90% reduction of EASI from baseline significantly improved after switching."
If one wishes to delve a little deeper into the potential why's - worth noting this article, shared here previously: Comparison of baricitinib, upadacitinib, and tofacitinib mediated regulation of cytokine signaling in human leukocyte subpopulations:
https://arthritis-research.biomedcentral.com/articles/10.1186/s13075-019-1964-1
3. A prognostic signature for lung adenocarcinoma by fivegenes associated with chemotherapy in lungadenocarcinoma:
direct .pdf https://onlinelibrary.wiley.com/doi/epdf/10.1111/crj.13723
"Results: Twenty-three differentially expressed genes (DEGs) were screened between LUAD samples and healthy samples, and BTK, FGFR2, PIM2, CHEK1, and CDK1 were selected to construct a prognostic signature. The OS of patients in the high-risk group (risk score higher than 0.69) was worse than that in the low-risk group (risk score lower than 0.69). Conclusion: The risk score model constructed by five genes is a potential prognostic biomarker for LUAD patients."
4. Unveiling COVID-19 Secrets: Harnessing Cytokines as Powerful Biomarkers for Diagnosis and Predicting Severity:
https://www.dovepress.com/unveiling-covid-19-secrets-harnessing-cytokines-as-powerful-biomarkers-peer-reviewed-fulltext-article-JIR
"In view of the above, new prognostic markers should be developed and included in routine clinical practice to effectively diagnose patients infected with the SARS-CoV-2 virus in different stages of the disease. The present findings indicate that the analyzed cytokines have potential diagnostic value for identifying patients with mild symptoms in the initial stage of COVID-19 and downregulating CS which has potentially life-threatening consequences. The research showed that IL-1ra, IL-2Rα, IL-6, IL-8, IL-12 p40, IL-16, and IL-18 levels serve as potential diagnostic biomarkers in COVID-19 patients. What is more, increased IL-1α levels proved to be valuable in assessing the severity of COVID-19."
Need a walk ;)
ATB
Man in the know, Jacob Plieth has tweeted https://x.com/JacobPlieth/status/1733949775261892940?s=20
link here.... https://www.oncologypipeline.com/apexonco/ash-2023-sense-and-serendipity-dizals-jackpot-win
Come on SAR, you know what to do.
ATB
Good morning Krusty, I am so sorry to hear this, my thoughts are with you, your wife and your family.
I am sure you have been thoroughly scouring the net for potential treatments & information. - accept my apologies if you have seen this already, and I am not trying to teach you how to suck eggs !
11.12.2023
Pfizer’s Elrexfio gets European marketing nod for treatment of relapsed and refractory multiple myeloma:
http://www.pharmabiz.com/NewsDetails.aspx?aid=165079&sid=2
ATVB, Take Care
Https://www.prnewswire.com/news-releases/dizals-golidocitinib-pivotal-trial-demonstrates-superior-and-durable-clinical-benefits-for-patients-with-rr-ptcl-in-oral-presentation-at-2023-ash-302010729.html
Or,
https://www.onclive.com/view/golidocitinib-demonstrates-efficacy-in-relapsed-refractory-ptcl
"The selective JAK1 inhibitor golidocitinib displayed antitumor activity and an acceptable safety profile in patients with refractory/relapsed peripheral T- Cell lymphoma (PTCL), according to findings from the pivotal phase 2 JACKPOT8 study (NCT04105010) presented during the 2023 ASH Annual Meeting."
Combined TYK2i/JAK1i read across.....?
This can only be good news!
ATB
1.
BMS Attributes Sotyktu Falling Short of Growth Expectations to Access, but Recent Spherix Global Insights’ Data Suggest Safety Concerns Are More of a Barrier to Increased Uptake:
https://finance.yahoo.com/news/bms-attributes-sotyktu-falling-short-170100131.html
2.
BMS Korea's psoriasis drug gets partial success in reimbursement challenge:
https://www.koreabiomed.com/news/articleView.html?idxno=22743
ATB
Https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2023.1271847/full#h4
"Multiple myeloma (MM) is a hematological malignancy characterized by an abnormal clonal proliferation of malignant plasma cells. Despite the introduction of novel agents that have significantly improved clinical outcome, most patients relapse and develop drug resistance. MM is characterized by genomic instability and a high level of replicative stress. In response to replicative and DNA damage stress, MM cells activate various DNA damage signaling pathways. In this study, we reported that high CHK1 and WEE1 expression is associated with poor outcome in independent cohorts of MM patients treated with high dose melphalan chemotherapy or anti-CD38 immunotherapy. Combined targeting of Chk1 and Wee1 demonstrates synergistic toxicities on MM cells and was associated with higher DNA double-strand break induction, as evidenced by an increased percentage of γH2AX positive cells subsequently leading to apoptosis. The therapeutic interest of Chk1/Wee1 inhibitors’ combination was validated on primary MM cells of patients. The toxicity was specific of MM cells since normal bone marrow cells were not significantly affected. Using deconvolution approach, MM patients with high CHK1 expression exhibited a significant lower percentage of NK cells whereas patients with high WEE1 expression displayed a significant higher percentage of regulatory T cells in the bone marrow. These data emphasize that MM cell adaptation to replicative stress through Wee1 and Chk1 upregulation may decrease the activation of the cell-intrinsic innate immune response. Our study suggests that association of Chk1 and Wee1 inhibitors may represent a promising therapeutic approach in high-risk MM patients characterized by high CHK1 and WEE1 expression."
ATB
Https://www.prnewswire.com/news-releases/technoderma-medicines-completes-phase-1-dose-escalation-clinical-trial-of-tdm-180935-for-atopic-dermatitis-302004584.html
"Arthur P. Bertolino, MD, PhD, MBA, Chief Medical Officer at Technoderma Medicines commented, "We are excited to see that TDM-180935 has met our expectations of a favorable safety profile in the current Phase 1 testing. As a potent JAK1/Tyk2 small molecule inhibitor, it may offer significant advantages regarding efficacy and safety compared to existing topical treatments for Atopic Dermatitis."
"This is a major milestone for the Company as we can now transition our second clinical program into Phase 2. We continue to build a robust and sustainable pipeline of drug candidates in multiple phases of clinical development," said Zengquan Wang, PhD, Chief Executive Officer at Technoderma Medicines. "We are well on our way to produce a portfolio of dermatology drug candidates."
About TDM-180935
TDM 180935 is a small molecule drug candidate being developed as a topical drug for treatment of Atopic Dermatitis. It functions as a potent JAK1/Tyk2 small molecule inhibitor. Preclinical assessment of TDM-180935 has demonstrated efficacy in multiple models and that it is well-suited for topical administration. Functional cell assays demonstrate that TDM-180935 can effectively suppress both keratinocyte- and T cell-derived pathogenic pathways characteristic for Atopic Dermatitis. Testing in rats and minipigs demonstrated favorable toxicology and toxicokinetic profiles. "
ATB
1.
https://www.medpagetoday.com/reading-room/acrr/psoriaticarthritis/107610
2.
Safety, Efficacy of Brepocitinib, a TYK2/JAK1 Inhibitor for Patients With Psoriatic Arthritis
– A close look at a marriage between Rinvoq and Sotyktu -- another first in class
https://www.medpagetoday.com/reading-room/acrr/psoriaticarthritis/107611
Food for thought ;)
ATB
7. JAK1 promotes HDV replication and is a potential target for antiviral therapy:
https://www.journal-of-hepatology.eu/article/S0168-8278(23)05230-3/fulltext
direct .pdf https://www.journal-of-hepatology.eu/action/showPdf?pii=S0168-8278%2823%2905230-3
8. Resolution of exacerbated rheumatoid arthritis-associated interstitial lung disease under baricitinib treatment:
https://www.tandfonline.com/doi/full/10.1080/03009742.2023.2274707?scroll=top&needAccess=true
9. Are All Janus Kinase Inhibitors for Inflammatory Bowel Disease the Same?:
https://www.gastroenterologyandhepatology.net/archives/december-2023/are-all-janus-kinase-inhibitors-for-inflammatory-bowel-disease-the-same/
10. Ursolic Acid’s Alluring Journey: One Triterpenoid vs. Cancer Hallmarks :
https://www.mdpi.com/1420-3049/28/23/7897
Good weekend all,
ATB
1. Janus-kinase inhibitors in dermatology: A review of their use in psoriasis, vitiligo, systemic lupus erythematosus, hidradenitis suppurativa, dermatomyositis, lichen planus, lichen planopilaris, sarcoidosis and graft-versus-host disease:
https://ijdvl.com/janus-kinase-inhibitors-in-dermatology-a-review-of-their-use-in-psoriasis-vitiligo-systemic-lupus-erythematosus-hidradenitis-suppurativa-dermatomyositis-lichen-planus-lichen-planopilaris-sarco/#st8
2. Identification and Biological Evaluation of a Potent and Selective JAK1 Inhibitor for the Treatment of Pulmonary Fibrosis:
https://pubs.acs.org/doi/epdf/10.1021/acs.jmedchem.3c01712
3. Leveraging synthetic lethality to uncover potential therapeutic target in gastric cancer:
https://www.nature.com/articles/s41417-023-00706-y
"GSSL analysis identified a total of 34 candidate synthetic lethal pairs, which included 33 unique targets. Among the synthetic lethal gene pairs, TP53-CHEK1 was selected for further experimental validation. Both computational and experimental results indicated that inhibiting CHEK1 could be a potential therapeutic strategy for GC patients with TP53 mutation."
4. Treatment patterns of systemic drug use in Japanese patients with plaque psoriasis: A retrospective chart review:
https://onlinelibrary.wiley.com/doi/full/10.1111/1346-8138.17038
5. Next generation JAK-inhibition strategies:
https://rheumnow.com/news/next-generation-jak-inhibition-strategies
"To stand out from the crowd, novel strategy or mechanism of action is fundamental. Data from combination JAK1/Tyk2 inhibition (TLL-018) were so impressive (i.e. no other advanced therapy could reach over 50% ACR50 response) that this was also head-scratching at the same time. Addition of Tyk2-inhibition to JAK1 appears to enhance treatment efficacy although this needs to be confirmed in definitive studies. "
6. TYK2 Is Essential for IFNα-Induced Resolution of MPN Features in a Murine Jak2V617F PMF Model:
https://www.sciencedirect.com/science/article/abs/pii/S000649712305468X
ATB
Good morning PCS1954, all is good here thank-you - I trust you are well! The mighty Hammers certainly don't do our health any favours, last nights' performance was abysmal, but a wins a win I guess, Soucek to the rescue again:)
Good luck & good health to all genuine holders & posters, you know who you are :)
Off for a data dig...
ATVB
Pertinent maybe, but a decent read either way:
https://lifescivc.com/2023/11/darkest-before-dawn-a-story-of-biotech-optimism-in-a-tough-market/
ATB
Https://www.fiercebiotech.com/biotech/roivant-ends-long-shot-lupus-program-after-phase-2-fail
ATB