[rosemountbomber]

Yep, home safe and sound. Funny about Tang and Kezar. They stopped the trial for LN and now FdA issuing a clinical hold. Would love to know Tang’s thinking on this.

[Whalatane]

Well hope U got out in time . Tang offers more than $1 a share for KZR ....will probably offer $10-$15 a share for AUPH .
Looks like he's trying for control of the severe LN market ...especially since VERA etc aren't pursing it
JMO
OMG. ...I just might have to buy some AUPH
Kiwi

[Whalatane]

For you Tang fans out there

$KZR Tang with a non-binding proposal to acquire 100% of the equity of Kezar Life Sciences, Inc. for $1.10 per share in cash, plus a CVR

https://archive.fast-edgar.com/20241008/ABBOQ22CIC22L2ZZ282R2MZZL8LQZ2Z2Z262/

Kiwi

[rosemountbomber]

No, opposite side of the state - 7 miles south of Daytona. Track of storm right now runs right through Orlando. Hoping it stays slow moving and our booked flight can get out Tues afternoon.

[Whalatane]

RMB. The Nephrologists my wife works with state their biggest problem is insurer push back due to cost of Lupkynis . Currently insurers in our area only want to cover for severe cases of LN where the patient has fairly rapid loss of kidney function ...ie for last best attempt ...and usually only for 6 mths .
Were you from the Tampa Bay Area ?.....looks to be pretty dicey next week
Good luck
Kiwi

[rosemountbomber]

Thanks for the article. I had previously seen it a while back and it is a good explanation of both drugs. However I guess it still comes down to what the person’s insurance co wants to do.

Yep, docked in Ft Lauderdale yesterday morning, rented a car and drove a couple of hundred miles north to spend the next few days seeing friends, etc where we spent 45 years of lives. Due to fly out of Orlando Tuesday afternoon, but now worried the approaching hurricane may throw a monkey wrench in that.

[Whalatane]

RMB. U might find this interesting
https://www.lupusencyclopedia.com/lupkynis-vs-benlysta-for-lupus-nephritis/

U back in the US or still aboard that floating Petri dish :--)

Kiwi

[rosemountbomber]

Do you think a potential acquirer will have that as a concern as well though. I suppose it would all depend on the price they would have to pay.

[Whalatane]

RMB Because of the expense of Lupkynis ...around $90k a yr ..insurers have major prior authorization hurdles often requiring Benlysta to be tried first . Benny is around $50k a yr and due to go generic in 2025

The patent for Benlysta is set to expire in the United States in 2025 and in Europe in 2026

Tangs a major AUPH player now and will definitely want a deal done before a generic Benny is available.

On September 6, 2024, TANG CAPITAL MANAGEMENT LLC (Trades, Portfolio) made a notable addition to its investment portfolio by acquiring 4,450,000 shares of Aurinia Pharmaceuticals Inc (NASDAQ:AUPH), a biopharmaceutical company based in Canada.Sep 12, 2024

JMO
Kiwi

[rosemountbomber]

Could that be the reason for reticence by potential buyers?

[moosedogger]

Don't they need a sale soon, hopefully before the end of the year?

Lupkynis is a drug owned by Aurinia Pharmaceuticals Inc. It is protected by 3 US drug patents filed from 2021 to 2023 out of which none have expired yet. Lupkynis's patents will be open to challenges from 22 January, 2025. Based on its patents and exclusivities, its generic launch date is estimated to be Dec 07, 2037. Details of Lupkynis's patents and their expiration are given in the table below.

Patent # US7332472 Cyclosporine analogue mixtures and their use as immunomodulating agents
Expires: Oct, 2024 (11 days from now)
Status: Active

Patent # US11622991 Protocol for treatment of lupus nephritis
Expires: Dec, 2037 (13 years from now)
Status: Active

Patent # US10286036 Protocol for treatment of lupus nephritis
Expires: Dec, 2037 (13 years from now)
Status: Active

https://pharsight.greyb.com/drug/lupkynis-patent-expiration

[moosedogger]

Kiwi- Thx for the explanation re KZR.
Hard to believe they were $30+ once!
Oh, wait....so were we
cheers

[moosedogger]

Why isn't the medical world listening?
They seem to be ZZZZZZZZZZZZZZZZZ..........................

Evaluating the cost-effectiveness of voclosporin for the treatment of lupus nephritis in the United States

CONCLUSIONS:

Following the inclusion of updated data in the cost-effectiveness analysis, voclosporin remains a cost-effective therapy for the treatment of active LN including in a Black, Hispanic, and Latino subpopulation, substantially below the ICER willingness-to-pay threshold of $150,000/QALY.

https://www.jmcp.org/doi/full/10.18553/jmcp.2024.23324

[Whalatane]

Moose. The overall renal response rate ( ORR ) was higher in KZR's P2 trial .

Kezar reports positive Phase II data of zetomipzomib for lupus nephritis
In the trial, 64.7% of the trial subjects attained an ORR, which is the primary efficacy endpoint of the study.

vs Lupkynis

The overall renal response rate (ORR) for LUPKYNIS was 41% at 52 weeks, compared to 23% for the control group receiving standard of care alone.

Hard to compare trials as KZR's was open label etc
KZR then ran into internal conflict on which program to advance and stock tanked .
When they finally go their LN program going again it was I believe as a P2b ( not a P 3 pivotal trial ) ...and have halted that trial due to safety concerns.

I usually only invest to biotech's running clinical trials ( Not Co's with approved drugs ...although I made an exception with ARDX recently ....and still hold a very small position in AMRN ( because I'm prescribed the drug and I'm an idiot ) )

Good luck with AUPH
Kiwi

[moosedogger]

I originally liked the KZR data better than the AUPH data

Wasn't the "data" only from a very small pt group; was it only about 5 people?

Can't remember but was puzzled why you liked it and thought it somehow superior to AUPH's

[Whalatane]

Even less competition for U now Jess

US-based biopharmaceutical company Kezar Life Sciences has suspended subject enrolment and patient dosing in the Phase II PALIZADE trial of zetomipzomib for active lupus nephritis.

The decision to suspend the trial was made following recommendations from an independent data monitoring committee (IDMC) after it had reviewed safety data from the trial.

I originally liked the KZR data better than the AUPH data ...but KZR ran into problems , stock crashed and now their last remaining serious LN trial has been suspended for safety reasons .

Kiwi

[Jesspro]

So, monopoly on best-in-class for many years to come and soon to be SOC, not too bad Kiwi. I don’t know why you’re not invested yet in this. Anyway, I hope we have a BO soon here. Good luck on your other stocks.

[Whalatane]

Jess. No mention of pursuing the LN indication at Vera's KOL day today . Next catalysts for AUPH likely to be Kidney Week at the end of October ( if they present anything ) and their next earnings report
Kiwi

[cervelo]

would be nice if we had a best case scenario, but no we are still stuck with pete, a low share price and time running out for a corner on the market. with pete at the helm the corner we will soon be on is a cardboard box on the corner of the freeway

[Whalatane]

Jess. VERA's Atacicept is already fast tracked for IgAN and will complete their P 3 in this kidney disease in Q2 2025 . They will announce Oct 2nd if they will pursue the LN indication ...using the same drug . If they pursue the LN indication I expect them to also seek a Fast Track designation for this indication as well.
So far Atacicept is the only drug shown to prevent decline in kidney function ( eGFR ) in IgAN . The other IgAN drugs just slow the decline .
Theres some 96 wk data due Q4 2024
So if they go into a P 3 for LN ....they will be using a drug thats already fast tracked and likely to have been approved for IgAN .... and on the market for IgAN by the time they finish the LN trial.
So it's definitely possible within 3 yrs to be approved as an expanded indication...... of a drug already being prescribed.

But as you have posted previously . The above is a best case scenario and theres a lot of ways this can derail .
I'm obviously long VERA and no position in AUPH ( although I think Tang is working to sell the Co )

Kiwi

[Jesspro]

Let’s for the sake of argument that VERA will conduct a p3 trial and that they think it’s successful and merits an approval from the FDA, the whole shebang will take at least a minimum of three years. Then there’s the issue of long term sustainability like Lupkynis’s sustainability of 3-years and counting. That is a total of 6 years minimum. You’ll probably have grandchildren by then.
There’s so many IFS Whala, but I hope they achieve it for kidney patients sake.

[Whalatane]

Jess

Vera Therapeutics to Host In-Person R&D Day in New York to Discuss Potential Indication Expansion for Atacicept on October 2, 2024

So you and any potential AUPH acquirer will know if VERA will advance into LN P3 trials on Oct 2nd
If they do..... it will be with a BAFF / APRIL compound similar to AUPH's newly launched P1 LN trial BAFF /APRIL compound.
Kiwi

[Jesspro]

LN landscape is littered with dead corpses of clinical trials. For patients sake, I hope you will be right with your 4th/5th/6th try.

[Scott999]

Ghosted the other board there eh Zzatty boy. I was just wondering is you could tell me how many Zzientists they have here. Looking to invest and thought I’d use your strategy of whether they have Zzientists here. Let me know. And don’t be a stranger on the other board. You’re dearly missed.

[cervelo]

yes he got that deal done

it did nothing for shareholder value and the 10 million was barely enough to cover is undeserved pay package for a year.
so it was a zero net value at present to the company and shareholders.

[Whalatane]

Well he got this deal done

Aurinia and Otsuka entered a collaboration and licensing agreement in December 2020 for the development and commercialization of oral voclosporin in the EU, Japan, the United Kingdom, Russia, Switzerland, Norway, Belarus, Iceland, Liechtenstein, and Ukraine.
As part of the agreement, Aurinia is eligible to receive a payment of $10 million U.S. dollars upon approval in Japan along with low double-digit royalties on net sales once launched.

Lupkynis just approved in Japan IIRC.

Lupy is an expensive drug with significant prior approval hurdles to overcome .
Suggest you watch the Oct 2 presentation by VERA where they are expected to announce if they will proceed with their BAFF/APRIL candidate into P 3 .
If they proceed with their P 3 , I suggest you celebrate if Tang is able to get you $12 a share on a buy out ...as I'm certain he will be celebrating
Kiwi

[cervelo]

he needs to be accountable to someone, tang is as good as we have seeing pettie has never felt accountable to shareholders who have funded this project as he rapes and pilfages the bank account.

better hurry before kamala taxes us on unrealized gains and increased capital gains tax
12 still moves me, 20 pays off my mortgage.
either way pettie walks with 10's of millions for a job never done

[rosemountbomber]

I believe the boxed warnings are the same but can’t be totally sure. In this release, similar to the UK, it indicates the boxed warnings in the EU, but the news releases for Japan does not give enough details: https://www.auriniapharma.com/investors-and-media/news-events/press-releases/detail/263/aurinia-announces-european-commission-approval-of

[Zeppo]

Question: Does the UK, the EU, and Japan have the same black box warnings as the U.S.? Is there flexibility in dosing?

[rosemountbomber]

Agree that that is the only way to interpret the massive buy by Tang. Good things to look forward to

[Whalatane]

Pete's works for Tang now . Tang is on the BOD and

On September 6, 2024, TANG CAPITAL MANAGEMENT LLC (Trades, Portfolio) made a notable addition to its investment portfolio by acquiring 4,450,000 shares of Aurinia Pharmaceuticals Inc (NASDAQ:AUPH), a biopharmaceutical company based in Canada.Sep 12, 2024

Tang is going to do a deal ...probably within a year ...and probably at less then the all time high in PPS .
Pete is just there to facilitate the deal ,Tang will force ( persuade ) on the BOD
JMO
Kiwi

[cervelo]

it matters not for us

as long as the BoD overrides shareholders votes and pete stays on the board and ceo this is nothing more than a penny stock
pete is running it with his 10 million draw a year.
pete is a plague to this stock.

[anbdpm]

Otsuka Receives Approval in Japan for Lupkynis® as a Treatment for Lupus Nephritis
RSS


Otsuka Pharmaceutical Co., Ltd. (Otsuka) announces that the Japanese Ministry of Health, Labor, and Welfare (MHLW) has approved Lupkynis® (voclosporin) for the treatment of lupus nephritis (LN), an inflammation of the kidneys caused by systemic lupus erythematosus, an autoimmune disease.

Lupkynis is a novel, oral immunosuppressive agent developed for the treatment of LN. It suppresses the immune system by inhibiting calcineurin, an enzyme that is crucial for the proliferation and activation of T cells, an important element of the immune system.

In the U.S., Aurinia Pharmaceuticals Inc. (Aurinia) received FDA marketing approval in January 2021 for Lupkynis as a treatment for active LN in adults. In September 2022 Otsuka received European Commission (EC) approval for Lupkynis as the treatment for active LN in EU member countries. Otsuka has subsequently received reimbursement in several EU countries as well as in the UK.

In December 2020, Otsuka and Aurinia announced that they entered into a collaboration and license agreement for the development and commercialization of oral voclosporin for the treatment of LN in Japan, the European Union (EU), and the UK, Russia, Switzerland, Norway, Belarus, Iceland, Liechtenstein and Ukraine.

Otsuka Pharmaceutical has been committed to research and development that contributes to patients and their families in order to meet unmet medical needs worldwide, focusing on cardiovascular, renal and autoimmune diseases as one of which are among our priority areas.



About lupus nephritis

Lupus nephritis (LN) is an inflammation of the kidneys caused by systemic lupus erythematosus (SLE). The kidneys are vital organs, and LN is an irreversible and progressive condition that puts them at risk for long-term complications. If left untreated, this kidney inflammation impairs kidney function and can lead to permanent kidney damage and even kidney failure, known as end-stage renal disease (ESRD). LN is one of the most serious complications of SLE.

In Japan, the number of SLE patients is estimated to be between 60,000 and 100,000, with women accounting for 90% of cases. It is particularly prevalent among women aged 20 to 40.1 Asians have a higher incidence of renal involvement compared to Caucasians, with 21% to 65% of Asian patients (living in Asia) with SLE having developed LN by the time of diagnosis, and 40% to 82% developing it over time.2 The development of LN in SLE patients often occurs at a relatively young age and is believed to increase the risk of end-stage renal failure, leading to a deterioration in life expectancy. The challenge is to achieve rapid remission of glomerulonephritis with reduction in proteinuria, while avoiding long-term use of high doses of steroid medication.



About the clinical trials AURORA 1 and AURORA 23, 4

The MHLW approval is based on data from clinical trials, including AURORA 1 and AURORA 2.

The AURORA 1 international phase 3 trial was conducted with the primary endpoint of renal response at 52 weeks. A total of 357 patients with active LN from age 18 to 75 were enrolled in the trial, of whom 179 patients and 178 patients were randomly assigned to the voclosporin and placebo groups, respectively.

Both the voclosporin group and the placebo group were co-administered with mycophenolic mofetil and oral steroids during the trial, with a regimen to reduce the dose of steroids. The proportion of patients achieving renal response at 52 weeks was significantly higher in the voclosporin group at 40.8% compared to 22.5% in the placebo group (p<0.001).

AURORA 2 evaluated the long-term safety, tolerability, and efficacy of voclosporin compared to placebo in 216 patients with LN (116 in the voclosporin group and 100 in the placebo group) who received an additional 2 years of treatment following completion of AURORA 1. The long-term safety and tolerability was assessed and no new or unexpected safety signals were observed.

Reference
1. Information Center for Rare Diseases https://www.nanbyou.or.jp/entry/53 (as of September 2024)
2. Jakes, RW. et al.:Arthritis Care Res. 2012; 64(2): 159-168
3. Brad H Rovin, Y K Onno Teng, et al. Efficacy and safety of voclosporin versus placebo for lupus nephritis (AURORA 1): a double-bling, randomized, multicenter, placebo-controlled, phase 3 trial. Lancet 2021; 397: 2070-80
4. Amit Saxena, Ellen M. Ginzler, et al. Safety and efficacy of long-term voclosporin treatment for lupus nephritis in the phase 3 AURORA 2 clinical trial. Arthritis & Rheumatology Vol. 76, No. 1, January 2024, pp 59-67

[Whalatane]

Z. as U know ...Lupkynis targets T cells . AUPH has begun their own BAFF / APRIL program for treating LN ...just several years behind VERA
Inhibiting both BAFF and APRIL is thought to be ( based on the past several yrs of research ) , a more effective way of inhibiting B cell production which is a key factor in developing Lupus Nephritis

Inhibiting B cells and T cells are both important therapeutic approaches in lupus nephritis (LN), but they target different aspects of the disease pathogenesis:
Inhibiting B Cells
B cells play a central role in LN pathogenesis through several mechanisms:
Production of autoantibodies, especially anti-dsDNA antibodies that can deposit in the kidneys and cause damage.
Acting as antigen-presenting cells to activate autoreactive T cells.
Secretion of pro-inflammatory cytokines.
Key approaches to inhibiting B cells include:
B cell depletion therapies like rituximab (anti-CD20 antibody).
Inhibition of B cell survival factors like belimumab (anti-BAFF antibody).
Targeting B cell signaling pathways.
Benefits of B cell inhibition:
Reduces autoantibody production and immune complex formation.
Decreases B cell-mediated T cell activation.
Can lead to long-lasting remission in some patients.
Inhibiting T Cells
T cells, especially CD4+ T helper cells, contribute to LN pathogenesis by:
Providing help to autoreactive B cells.
Producing pro-inflammatory cytokines like IL-17.
Infiltrating the kidneys and causing local inflammation.
Approaches to inhibiting T cells include:
Calcineurin inhibitors like tacrolimus.
Costimulation blockade (e.g., abatacept).
Targeting specific T cell subsets like Th17 cells.
Benefits of T cell inhibition:
Reduces T cell-dependent B cell activation and antibody production.
Decreases inflammatory cytokine production.
Can be effective in cases resistant to B cell-targeted therapies.
Comparison
B cell inhibition tends to have a more direct effect on autoantibody production, while T cell inhibition affects broader immune activation.
B cell-targeted therapies like rituximab and belimumab have shown efficacy in clinical trials for LN, while T cell-targeted approaches are still being investigated.
Some newer approaches aim to target both B and T cells simultaneously, recognizing the complex interplay between these cell types in LN pathogenesis.
In conclusion, both B cell and T cell inhibition strategies have shown promise in treating LN. The choice between them often depends on the specific disease characteristics and patient factors. Combination approaches targeting both cell types may offer synergistic benefits in some cases.

How do B cells contribute more significantly to lupus nephritis compared to T cells
B cells appear to contribute more significantly to lupus nephritis compared to T cells in several key ways:
Production of pathogenic autoantibodies: B cells are the precursors to plasma cells, which produce autoantibodies that are central to lupus nephritis pathogenesis. Anti-dsDNA antibodies in particular can deposit in the kidneys and cause direct tissue damage.
Formation of immune complexes: The autoantibodies produced by B cells form immune complexes that deposit in the kidneys, triggering inflammation and tissue injury.
Cytokine production: B cells produce pro-inflammatory cytokines that contribute to the inflammatory environment in lupus nephritis.
Antigen presentation: B cells can act as antigen-presenting cells to activate autoreactive T cells, perpetuating the autoimmune response.
Infiltration of kidneys: Studies have shown increased infiltration of B cells and plasma cells in the kidneys of lupus nephritis patients and mouse models.
Correlation with disease activity: The number of circulating plasma cells correlates with lupus disease activity and anti-dsDNA antibody levels.
While T cells also play important roles in lupus nephritis, their contributions appear to be more supportive:
Providing help to B cells for autoantibody production.
Producing inflammatory cytokines.
Infiltrating the kidneys to cause local inflammation.
However, the direct tissue damage and formation of immune complexes mediated by B cell-produced autoantibodies seem to be more central to the pathogenesis of lupus nephritis. This is supported by the efficacy of B cell-targeted therapies like rituximab in treating lupus nephritis.

In summary, while both B and T cells contribute to lupus nephritis, the ability of B cells to produce pathogenic autoantibodies and form immune complexes that directly damage the kidneys appears to make their role more significant in the disease process.

Role in pathogenesis:
BAFF and APRIL levels are elevated in patients with systemic lupus erythematosus (SLE) and LN.
They contribute to B cell hyperactivity and autoantibody production, which are central to LN pathogenesis.
Overexpression of BAFF in mice can induce lupus-like symptoms, including glomerulonephritis.
Therapeutic targets:
Inhibiting BAFF and/or APRIL has become a promising treatment strategy for LN.
Several drugs targeting these cytokines have been developed and tested in clinical trials.
Specific treatments:
Belimumab: A BAFF inhibitor approved for treating SLE, including patients with LN.
Atacicept: A dual BAFF/APRIL inhibitor that has shown potential in clinical trials for SLE and LN.
Telitacicept: Another dual BAFF/APRIL inhibitor being investigated for various autoimmune diseases, including LN.
Advantages of targeting BAFF/APRIL:
More specific than traditional immunosuppressants, potentially offering better efficacy and safety profiles.
Addresses the underlying B cell-driven pathogenesis of LN.
Biomarkers:
Serum levels of BAFF and APRIL may serve as biomarkers for disease activity and treatment response in LN.
Ongoing research:
Studies are exploring the optimal use of BAFF/APRIL inhibitors, including combination therapies and identifying patient subgroups most likely to benefit.

In summary, BAFF and APRIL inhibition represents a targeted approach to treating LN by addressing the B cell-mediated aspects of the disease. While some treatments like belimumab are already approved, research continues to optimize the use of these therapies and develop new agents targeting this pathway.

So we should know Oct 2nd if VERA is willing to spend the millions required to advance their LN BAFF / APRIL into a P 3 trial .........so no worries till then

Kiwi

[zzaatt]

P3 LN drug ( Baff /April combo ) which is expected to be better than AUPH's Lupkynis

Expectations are rarely met in the biotech arena. I woudn't worry too much.