So imagine if every bolt weapon had this keyword called "Bolt" with a rule like this: "If the enemy unit you are targeting has a toughness characteristic worse than the strength characteristic of this weapon, increase the AP characteristic of this weapon by 1."
It would make the lower level bolt weapons even better at dealing with infantry, while weapons like the Heavy Bolter would be able to be better at taking out elite infantry.

hi,
here is the Snap-on Datasheet. It is in google sheet format.
https://docs.google.com/spreadsheets/d/1AOiflz5mmKKkqUPM2rQMrmGujCGFFDHClcjXGRaJklY/edit?usp=sharing
Just a recap,

1. this is a very high quality tools maker, that has been around for 104 years. Their tools are really expensive and highly respected in the automotive industry.
2. High quality because their Revenue and Earnings are very consistent except for a slight decline in 2019 and 2020 in the last ten years. High quality also because their rokker metrics are between high teens to 20s. (ROA, ROE, ROIC, ROCE)
3. Historically, they have growing at 3-6% revenue and about 9-12% for EPS. However, they are experiencing problems with revenue growth and the street "was" pricing them like a 1.4% earnings growth company. In their recent earnings call, they missed the guidance and the stock dropped about 6% before recovering to pre-earnings level. The CEO said in the earnings call that from what he is seeing this is similar to COVID and Great financial crisis and it will take 2 - 3 quarters to go back to historical levels. Independent mechanics are pausing large ticket items until they see clarity on where the economy is going.
4. If you believe that people are driving their cars longer, currently at 12.5 years, then the long term future for SNA is quite assured.

(disclosure, i do not own any SNA stock, it is in my watchlist)
(note on the datasheet: I removed my valuation process, just the results, and added my comments)

Any older siblings out there really feel when Dan tells Cox he needs to stop destroying JDs love of medicine. It gets me every time and its one of my favorite scenes. I often think its because im the older sibling and like Dan ive protected my younger sibling many a time and very rarely if ever i get any thanks or acknowledgement but we do as we are taught to be grown up from the get go and look after that sibling. Our siblings often like Dan arent looked up to. We are the experiments, the prototypes for the next ones.
I dont know i just love how he wakes Cox up. He does something everyone else is afraid of and thats not just stand up to Cox but even low level threaten him to buck up his ways. I just love the scene. there isnt violence its just one man telling home truths to another. Making them wake up
“Hey, listen, Dr. Cox. No offense. I'm a big fan of the tough guy act. But let me tell you what I really think. I think you love the fact that these kids idolize you. Johnny does! Johnny was always the one in the family we knew was going someplace. Sweet kid, smart kid. Becoming a doctor? This is all he ever wanted. And yet somehow, you found a way to beat that out of him, haven't you? Turned him into some kind of cynical guy, who seems to despise what he does. Dr. Cox... Johnny's never gonna look up to me. Ever. But he hangs on your every word. So, I'm asking... I'm telling you: Take that responsibility seriously; stop being such a hard ass. Otherwise, you're gonna have to answer to me.”

New Stuff Added
Trying to get rid of some manga. condition varies some brand new, some very used and are priced accordingly.
Open to offers.
Shipping not including. if you buy enough then I will pay for shipping.
Tried to price things best I could if you believe pricing isn't fair and you're interested we can work something out.
Signed Funko! at the bottom.
Thanks for looking!
Photo Link: Image/Proof
Manga Lots 3+ Volumes:
A, A tropical fish yearns for snow vol 1-3 15$
B, Bloody Mary vol 1-4,6 30$
Bride of the water god vol 1-9 90$
C, Chainsaw Man BAM Box set vol 1-4 (With Poster) 20$
D,
E,
F,
G,
H, Hi score girl vol 1-8 50$
I,
J,
K, Kare kano vol 8,11-14 25$
L,,
M, Mashle vol 1-3 15$
N, Naruto Vol 8-10,12-13,26-28,39,41-43,50 (13 Volumes Total) 45$
O,
P,
Q,
R,
S, Shaman King Singles Vol 1,2,2,3,3,5,7,7,8,8,12 6$ Each

Saint young men HC vol 1-3 36$ 

T, Testarotho vol 1-4 Complete 30$
The Saviors book Cafe story in another world vol 1-5 Complete 45$
U,

Uzumaki Junji ito singles vol 1-3 (Complete) 50$ (Check condition) 

V,
W,
X,
Y,
Z.
Manga Lots with 1-2 Volumes:
A,
A distant Neighborhood Singles vol 1-2 Complete 20$
B,
Beast Complex Vol 1 7$
Blue Period vol 1-2 15$
C,
Citrus vol 1,6 15$
Code Geass vol 1 15$
Captain Harlock vol 2 HC 10$
20th Century Boys Singles vol 2 10$
D,
Dragon Head vol 7 20$
Dragon Ball Z vol 7 4$
Drrr!! Vol 1 7$
E,
F,
Full Metal Panic! Vol 1 8$
Firefighter daigo vol 4 15$
G,
Golden Kamuy vol 1 8$
H,
Happy Mania vol 1 15$
Hells Paradise vol 1 8$
Hi Score Girl Vol 1 6$
I,
Inside Mari vol 9 8$
Iron wok jan! Vol 4 12$
J,
Jujutsu Kaisen vol 1 (Spine Miss Print) 3$
Jing:King of bandits vol 7 3$
K,
Kamisama Kiss vol 7 8$
Kaiju NO.8 Vol 1 8$
Kodocha Vol 5 9$
Knights of sidonia singles vol 4 10$
King of cards vol 4 10$
L,
Look Back vol 1 8$
Lupin 3 Singles Vol 1 12$
M,
Mashima Heros 7$
My Hero academia smash vol 1 5$
N,
Naruto the Official fanbook 6$
Naruto Forever The unofficial Guide 6$
Naruto Full Color Movie Manga 6$ each
Nightmare inspector vol 4 4$
No man's land vol 1-2 Complete 10$
O,
One Piece Gold Foil vol 4 12$
Oh my goddess vol 31 8$
Oh my goddess vol 19,19,19,19 20$ Each
P,
Prison school Vol 14 13$
Phantom Tales of the night vol 1 8$
Q,
R,
Records of Ragnorok vol 1 8$
S,
Sayonara Football Volume 1 8$
Solo Leveling Vol 1-2 26$
sweetness and lightning volume 1 7$
Scums Wish Vol 1 18$
Sweat and Soap vol 1-2 14$
Steins Gate Vol 1 Loot Crate Exclusive 20$
Stellvia vol 1-2 10$
Shortcake cake vol 1 6$
Shaman king omnibus vol 1 10$
Saiyuki vol 1 HC 12$
T,
Testament of sister new devil vol 1 30$
The Last Uniform Vol 1 10$
Tokyo Knights vol 1 3$
Tokyo tribes vol 3 6$
U,
V,
Vampire Hunter D Vol 2 7$
W,
Wotakoi B&N Exclusive vol 1 10$
X,
Xo Genasys vol 1 6$
Y,
Yowamushi Pedal Loot Crate Exclusive Vol 1 10$
Yakitate!! Vol 6 4$
Yona of the dawn vol 1,34 12$
Z.



Manga Light Novels:
A,
B,
C,
D,
E,
F,
G,
Goblin Slayer LN Vol 1 7$
H,
I,
J,
K,
L,
M,
My Youth Romantic Comedy Is WRONG as I expected Ln Vol 1-2 15$
Monster Girl Doctor Ln Vol 1 6$
N,
Naruto Mission protect the waterfall village! Ln 6$
Naruto Innocent Heart,Demonic Blood Ln 6$
No Game No life LN vol 1 7$
O,
P,
Q,
R,
Re: Zero Ln Vol 1 7$
S,
Spice&Wolf Ln vol 1-14 120$
T,
The Alchemist Who Survived Now Dreams Of Quiet City Life Ln Vol 1-2 15$
The Saga of the tanya of evil Ln Vol 1 8$
The Saga of the tanya of evil Ln Vol 1 8$
Toradora Ln Vol 1 8$
The twelve kingdoms Ln 7$

U,
V,
Vampire Hunter D LN vol 2 10$
W,
X,
Y,
Z.
Signed Funko!
Jiraiya On Toad Hot Topic Exclusive Signed By David Lodge (Long Quote) PSA Cert #73 200$
Ahsoka Amazon Exclusive Signed by Rosario Dawson JSA Cert #467 300$
Demon slayer funko pops 6 total (2 not signed) 290$
Photo: Images/Proof

Welcome, beautiful people of wicked_edge, to the inaugural installment of The People’s Republic of Croap - my latest review series wherein I evaluate, pontificate upon, and review soaps, creams, and croaps that have a connection to China. Too long has the world not seen the glory of Chinese wetshaving artisans and my review series aims to rectify that injustice. The contributions China has given to wetshaving are vast. The overwhelming majority of all badger hair used in shaving brushes is sourced from China. Nearly all synthetic fibers in synthetic hair brush knots were also pioneered and developed by Chinese cosmetic companies. Resin materials used for brush handles are primarily manufactured by Chinese industrial companies. Millions of razors are produced every year by Chinese companies for entry-level and high-end razor brands spanning from the Maggard Razor store-brand heads, all the way up to Aylsworth’s APEX AL, APEX SS, and Kopparakant razors. And yet rarely is the soapmaking prowess of China’s artisans contemplated. So now we will embark on a journey to the East, with me as your monkey king, and together we will discover the boundless wealth of high quality wetshaving software that hails from mainland Taiwan China.

Aren’t you retired from posting? Why didn’t you stay retired?

For better or for worse, on April 3rd, in the two thousand and twenty fourth year of our Lord, I hijacked a thread that should have been the opportunity for this amazing community here at wicked_edge to join creative forces with the community’s preeminent buyer of women’s panties, the man who ended the base race, the man who wanted to create a sub exclusive (which by all accounts is still happening) that would finally make barbershop scents interesting again: u/bostonphototourist. In subsequent groveling negotiations on another chat platform, I joined forces with likeminded individuals to harangue Will into conceding request that Barrister and Mann revisit the legendary scent Roam, and out of that discussion came the a seed of an idea that would become Roam 2: Yes. Really. in a vegan version of the legendary Omnibus shaving soap base. My part in these negotiations was the threat offer that I would “un-retire” from my legendary career as a shitposter community icon. Well Roam 2 is confirmed for release on June 4, and I am nothing if not a man of my word. So here we are.

Enough about you, what about the soap reviews?

Those of you familiar with my review methodology know that everything I evaluate is objective and scientifically proven. Those of you unfamiliar with my review methodology can kick rocks.
Scoring will be conducted based on my interpretation of the Four Cardinal Principles derived from the Legalist text Guanzi, attributed to the Qi philosopher Guan Zhong.

• Lǐ (禮) - the rites, ritual; how does this soap engage with the ritual of wetshaving?
  
• Yì (義) - righteousness; does this soap behave appropriately and without deception?
  
• Lián (廉) - integrity; is the soap upright in its behavior?
  
• Chǐ (恥) - shame; how does this soap acknowledge its faults?
  

Twoface Brothers Shaving Cream - Classic

For the inaugural soap of this review series, I could choose no better subject than Classic, a shaving cream from Beijing-based Twoface Brothers. The brainchild of Master Chen, Twoface Brothers is a high-end, luxury barbershop at the absolute pinnacle of classic barbershop style. Twoface Brothers is also a line of wetshaving products, including a unique shaving cream formulation that is offered in four scents: Classic, Everest, Tobacco, and Rum. I purchased a tub of 3, to the exclusion of Tobacco due to the scent note, “cigarettes,” though I have been informed this may have been a translation confusion and that it does not smell like straight cigarettes. Twoface Brothers recently partnered with Oumo to offer their line of shave creams, aftershaves, and preshave oil to international customers outside of China. The branding is an elegant combination of East-meets-West style considerations.
Lǐ (禮) - the rites, ritual; how does this soap engage with the ritual of wetshaving? Unusual/5
The cream is truly a cream, with the consistency of whipped cream cheese. If you were to swirl your brush in this shaving cream like you would with a hard soap, you would scoop up cream as if your brush was a spoon. This disrupts the customary ritual of loading soap into your brush.
Yì (義) - righteousness; does this soap behave appropriately and without deception? 110%
This soap builds into a lather very well, able to take quite a bit of water and with appropriate thickness and stickiness that it remains solidly on your face while the brush works it into a rich, foamy lather.
Lián (廉) - integrity; is the soap upright in its behavior? 10/10
The lather retains moisture well and is incredibly slick once hydrated. The scent is of good strength, and Classic smells very good to my nose.
Chǐ (恥) - shame; how does this soap acknowledge its faults? 2/3
The tin lid, designed for impeccable aesthetics, is susceptible to denting around the rim. Unfortunately mine was dented while in transit to the United States from China.
Final Verdict: 13.1+Unusual/19
Disclosure: I buy all my soaps, either new at full price, used, or on clearance. Ain’t no soaper out there gonna send me free stuff. Get off my jock.

Two years ago (2022) in mid August, I got sexually assaulted by my mom‘s boyfriend. Now what happened may not be as bad as what many others have experienced, but I guess the worst part of it was how my mom and my family “handled” it.
He was a chain-smoking alcoholic and that day my mom and him were telling me about all the bad guys in college and how I have to be careful they might sexually assault me or bully me or whatever. At the end of the conversation, my mom told me to fix my hair in her closet/makeup room and that’s what I did. My mom went downstairs to cook, and I don’t know what her boyfriend was doing, but he kept popping in saying he was just trying to help me, call him up, he’s just trying to show me. He and I had already been on bad terms since we met during Covid. He was her client and he just got out for a DUI. We’d argue a lot, and my mom really didn’t do anything about it.
FYI, he kept trying to kiss me on the lips, but my mom would argue till the day she dies that all he did was kiss me on the cheek. He groped my left boob, I told her this while cupping it. She’d say that he held my side. She wasn’t in the room. She was downstairs cooking and I was screaming. Every time he would come in trying kissing me and, every time she would scream at him too even though she was downstairs because she heard me. At one point she came up so I told her that he’d been trying to kiss me but she thought it was on the cheek so she went back downstairs. Same shit—he comes in saying crazy ass shit, tries kissing me on the lips while my mom and I scream at him… except this time he gropes me, says sorry when he leaves the room and I rush downstairs telling my mom what happened. I was using the flat iron and I had every opportunity to burn him. Honestly a part of me wishes I did but it wasn’t the answer to this situation; it would’ve made things worse for me so I’m glad I didn’t do anything like that. When I went to college I used the resources available to me but I made no tangible improvements or positive effects for my life. I even went straight to the Police Department (not just UPD) I could’ve gotten a restraining order but I didn’t. The officer even asked me point-blank, “So are we arresting this guy?”
I remember on my last day to work that summer (2022), I was talking to my mom and she was asking me if I really wanted to tell anyone about it like it was a bad thing. The same thing happens a few days later when I get my outpatient surgery, she reminds me of her “handling” the situation. Nobody in my family really gives a fuck btw, when I told my relatives what happened they kind of danced around it, were in disbelief and honestly, were kind of telling me that they didn’t believe me. When I told my brother he said straight up that he didn’t believe me he didn’t think anyone else would.
My moms boyfriend doesn’t drink or smoke to that extent anymore. I still don’t wanna be around him, but I don’t have money. I don’t have friends. I can’t just get an apartment and my mom gets very angry at me when I had a summer job (2023) that despite paying for my stay at college and you guessed it, was over the summer, she was mad that I didn’t just stay at her house. Get a seasonal job here and make money here for free! Because he just won’t bother me, she says. I get free transportation both here and there. I don’t wanna go on family trips because he’s always there. I don’t even want to be in the same room as him. She says I’m segregating and making people walk on eggshells. My mom is so pissed about it that she won’t bother keeping us in separate areas. She says I’m segregating and making people walk on eggshells.
Isn’t that the worst part? I still live here. This is my permanent address. Like, I came back here for the summer break, for the winter intercession, and the gap of time before my last summer internship. I have epilepsy. I can’t get a job rn and I can’t make friends bc my people skills are disgustingly bad. I depend on my mom to drive me to my pharmacy. I don’t speak to any of my family because of how they responded to this situation + he’s at every event. Of course everyone loves him. I don’t love my mom, but I tell her I do so I can be on some “positive” level with her, even though we argue almost daily. She has no sympathy, despite saying her childhood was much worse—she loved her mom so much that she’d speak to her every day... like it’s some competition. She doesn’t understand why her kids at various times in their lives have become estranged from not only her, but her side of my family (one is 100% estranged). I can’t forgive anyone.

Hi, this is my first post so I’m not sure if I’m doing this right. But I’d really appreciate your advice or assurance. I (23F) met my (25M) boyfriend in the United Kingdom this year, we have been dating for 8 months . For context, I’m from the U.S. I was on a visitor visa and we fell in love; I applied to grad school for this next year in his country and I got in. However, I am unable to afford grad school and on the salary of the job I am going to school for, loan repayments and rent would take all of my paycheck, making life pretty difficult for me. My boyfriend, who has been really encouraging of the grad school plan said that in light of the loan issue that I should stay home, work, and save money until we are ready to get married. The problem is, he’s wanting to wait 1-2 years. If I was living in the same country I’d be okay with waiting and taking things slow, but I’m worried that if we’re apart for that long with only a few visits ( we’d only be able to take a few weeks off at a time) per year we’d fizzle out and never end up being together. I love him so much and I’m trying so hard to get to be with him. I’m looking into work visas, I’m trying everything. Those who have been together in a long distance relationship longer than I have, any advice to make sure we don’t fizzle? We talk almost every day but I’m starting a new job soon where I’ll be very busy. Thanks so much, sorry if I sound very disconnected, I just got the loan news today.

If you think we’d get on, message!
Make sure you board this train before it eventually crashes and I vanish off into the mountains and live in a remote cabin or some shit, probably dancing like Jamiroquai and doing head spins.
I'm 26 from the United Kingdom and a musician (guitarist, singer and songwriter)
Generally looking for people to talk to, get to know and have fun. Maybe even meeting one day, who the hell knows.
Like almost everyone in the world, I love films, music and having a good time. You'll often find me at gigs and festivals getting asked to crouch a bit because I'm apparently too tall.
Actual real life reviews
1) how can one person possibly be this dazzling 2) 11/10 would talk to again 3) The matrix wasn't a true story, are you a moron? 4) Who are you and why are you in my house!
Interesting fact about myself - I've had a few of my songs played on various BBC stations.
I’m great at holding a conversation so doesn’t matter if you’re super confident or shy, just send me a message and I'll reply.
Post is open to all countries, so come violate my DMs 📩

~RIGL Thesis – 5/18/2024~
Outstanding Shares 175M
131 Institutional Holders
111,129,461 Total Shares Held
63.36% Institutional Ownership
Total Cash on Hand 3/31/2024 = $49.6M
Total Debt: $101.5M
Cash Burn Approximate = $8M per quarter (6 quarters of cash without any increases in revenue)
Q12023 REV = $26M
Q22023 REV = $26.8M
Q32023 REV = $28.1M
Q42023 REV = $35.8M
Q12024 REV = $29.5M (Decline from Q4 likely from end of year versus new-year tracking of Rx and shipments of drugs, resetting of Copays)
Most Recent EPS -$0.05 per share
May 22, 2024 - Vote on S will take place, caution
~Statistics Applicable To Thesis~
333.3 million US Population (2022)
8,109,679,892 Global Population (2024)
~Drugs On Market~
~Tavalisse – Treatment for ITP, FDA Approved April 17, 2018~
~What is ITP?~
Immune thrombocytopenia (ITP) is an illness that can lead to bruising and bleeding. Low levels of the cells that help blood clot, also known as platelets, most often cause the bleeding.
Once known as idiopathic thrombocytopenic purpura, ITP can cause purple bruises. It also can cause tiny reddish-purple dots on the skin that look like a rash.
Children can get ITP after a virus. They most often get better without treatment. In adults, the illness often lasts months or years. People with ITP who aren't bleeding and whose platelet count isn't too low might not need treatment. For worse symptoms, treatment might include medicines to raise platelet count or surgery to remove the spleen. Immune thrombocytopenia (ITP) - Symptoms and causes - Mayo Clinic
~What is Tavalisse?~
TAVALISSE is a prescription medication used to treat adults with low platelet counts due to chronic immune thrombocytopenia (ITP) when a prior treatment for ITP has not worked well enough. It is not known if TAVALISSE is safe and effective in children.
The cost for Tavalisse oral tablet 100 mg is around $15,404 for a supply of 60 tablets, depending on the pharmacy you visit. Quoted prices are for cash-paying customers and are not valid with insurance plans. This price guide is based on using the Drugs.com discount card which is accepted at most U.S. pharmacies.
Tavalisse Prices, Coupons, Copay & Patient Assistance - Drugs.com
TAVALISSE IS AN ORAL MEDICATION TAKEN TWICE DAILY WITH OR WITHOUT FOOD¹
A 12-week evaluation period is recommended
60 tablets = 1 month supply, evaluation period = 3 months, Cost for 3 months = $46,212 Cash, assuming cheaper through wholesale, insurance, discount cards, etc.
Dosing TAVALISSE® (fostamatinib disodium hexahydrate) tablets (tavalissehcp.com)
~Addressable Market~
“Our findings suggest that nearly 20,000 children and adults are newly diagnosed with ITP each year in the US, substantially higher than previously reported. Among patients requiring formal medical care, the economic burden during the first 12 months following diagnosis is high, with estimated US expenditures totaling over $400 million.”
Primary immune thrombocytopenia in US clinical practice: incidence and healthcare burden in first 12 months following diagnosis - PubMed (nih.gov)
The estimated prevalence of ITP in the United States is 9.5 per 100,000 people, with a global prevalence of over 200,000 people at any given time [1].
Immune thrombocytopenia. [ Oct; 2022 ]. 2022. https://rarediseases.org/rare-diseases/immune-thrombocytopenia
~Author Calculations/Estimates~
ITP estimated cases based on measured statistics 31,635 cases a year in the US and 770,355 cases globally each year.
~Rezlidhia – R Acute Myeloid Leukemia, FDA Approved December, 22, 2022~
~What is Relapsed or Refractory Acute Myeloid Leukemia?~
Relapsed, or recurrent, acute myeloid leukemia (AML) means the leukemia has come back after treatment and remission.
Refractory AML means the leukemia did not respond to treatment. Complete remission has not been reached because the chemotherapy drugs did not kill enough leukemia cells.
Both relapsed and refractory AML need more treatment to reach complete remission.
Your healthcare team will suggest treatments based on your needs and work with you to develop a treatment plan. Some factors considered for your treatment include:
your age
your health
how long the leukemia was in remission
treatments you had before
where the leukemia comes back
Treatment options usually include chemotherapy and a stem cell transplant if possible. Targeted therapy may also be used.
Treatments for relapsed or refractory acute myeloid leukemia Canadian Cancer Society
~What is IDH1?~
Somatic mutations in isocitrate dehydrogenase (IDH) genes occur frequently in adult Acute myeloid leukemia (AML) and less commonly in pediatric AML… Enhanced genomic and epigenomic profiling of acute myeloid leukemia (AML) has led to identification of recurrent mutations that are prognostic and are candidates for targeted therapy. Somatic mutations in isocitrate dehydrogenase (IDH) genes, IDH1 and IDH2, occur in ∼6% to 16% and ∼8% to 19% of adult patients with AML, respectively.^1-5 In pediatric AML, IDH mutations are rare, occurring in <4% of patients.^6-11
Characteristics and prognostic impact of IDH mutations in AML: a COG, SWOG, and ECOG analysis Blood Advances American Society of Hematology (ashpublications.org)
~What is Rezlidhia?~
REZLIDHIA is a prescription medicine used to treat adults with acute myeloid leukemia (AML) with an isocitrate dehydrogenase-1 (IDH1) mutation when the disease has come back or has not improved after previous treatment(s).
Targeted Treatment REZLIDHIA® (olutasidenib) capsules
The cost for Rezlidhia oral capsule 150 mg is around $17,468 for a supply of 30 capsules, depending on the pharmacy you visit. Quoted prices are for cash-paying customers and are not valid with insurance plans. This price guide is based on using the Drugs.com discount card which is accepted at most U.S. pharmacies.
Rezlidhia Prices, Coupons, Copay & Patient Assistance - Drugs.com%20is%20a%20member,on%20the%20pharmacy%20you%20visit.)
~Addressable Market~
The annual incidence of new cases in both men and women is approximately 4.3 per 100,000 population, totaling over 20,000 cases per year in the United States alone.[13] The median age at the time of diagnosis is about 68, with a higher prevalence observed among non-Hispanic Whites. Furthermore, males exhibit a higher incidence compared to females, with a ratio of 5:3.
Acute Myeloid Leukemia - StatPearls - NCBI Bookshelf (nih.gov)
~Author Calculations/Estimates~
Cases of AML with IDH1 would be 11% based on the median of statistics above (6% to 16%) leaving approximately 1500 to 2000 cases a year in the US. Appling the same calculations to world population would amount to approximately 38,500 cases a year globally.
~Gavreto – Treats RET+ Non-Small Cell Lung Cancer In Adults and RET+ Thyroid Cancer in Kids and Adults, FDA Approved August 9, 2023~
For the sake of common ground, I am going to assume these types of cancers do not need to be elaborated on as we all likely have a basic understanding of what they are. The medical conditions treated by Tavalisse and Rezlidhia I felt needed a more in-depth explanation because they are not common. I will elaborate on RET+ a little later in this writing.
~What is Gavreto?~
GAVRETO is an oral once daily prescription medicine used to treat certain cancers caused by abnormal rearranged during transfection ~(RET+)~ genes in:
Adults with non-small cell lung cancer (NSCLC) that has spread
Adults and children 12 years of age and older with advanced thyroid cancer or thyroid cancer that has spread who require a medicine by mouth or injection (systemic therapy) and who have received radioactive iodine and it did not work or is no longer working*
It is not known if GAVRETO is safe and effective when used to treat cancers caused by abnormal RET genes in children for the treatment of NSCLC or in children younger than 12 years of age for the treatment of thyroid cancer.
Home GAVRETO® (pralsetinib)
The cost for Gavreto oral capsule 100 mg is around $11,745 for a supply of 60 capsules, depending on the pharmacy you visit. Quoted prices are for cash-paying customers and are not valid with insurance plans. This price guide is based on using the Drugs.com discount card which is accepted at most U.S. pharmacies.
The recommended dosage for adults and children 12 and over is 400mg orally once daily. Each capsule is 100mg, which means you will take 4 capsules. Gavreto should be taken on an empty stomach, at least 1 hour before or 2 hours after a meal.
Gavreto Prices, Coupons, Copay & Patient Assistance - Drugs.com
~What is Rearranged During Transfection Positive (RET+)?~
RET-positive cancer is caused by a mutation or abnormal re-arrangement of the RET gene. It occurs most commonly in lung cancer and several types of inherited and sporadic thyroid cancers. RET alterations also occur in an estimated 1-2% of multiple other cancers, including ovarian, pancreatic, salivary, breast, and colorectal cancers.
RETpositive Empowering Patients and Driving Research
Rearranged during transfection (RET) rearrangements were first identified as oncogenic drivers in NSCLC in 2012. The proportion of patients with NSCLC who have RET rearrangements (ie, fusion-positive disease) is approximately 1%-2%.
RET Fusion-Positive Non-small Cell Lung Cancer: The Evolving Treatment Landscape The Oncologist Oxford Academic (oup.com)
RET alterations occur most commonly in lung cancer (non-small cell lung cancer (NSCLC)) and the number of new cases diagnosed each year is considerable, accounting for approximately 37,500 [IG1] cases worldwide and 4,000 cases in the US (2% of NSCLC) (2,3). RET alterations are also common in several types of inherited and sporadic thyroid cancers and can occur in other types of cancers like ovarian, breast, pancreatic, and colorectal cancers, among others (4-8) adding >110,000 cases yearly worldwide (9).
What is RET Positive Lung Cancer? - The Happy Lungs Project
(2) Although medullary thyroid carcinoma represents 5-10% of all thyroid cancers, activating RET gene abnormalities occur in over 90% of hereditary and approximately 40%-60% of sporadic medullary thyroid carcinoma cases.
Patients – RETpositive%20Although%20medullary%20thyroid%20carcinoma,sporadic%20medullary%20thyroid%20carcinoma%20cases.)
~Prevalence of Non-Small Cell Lung Cancer~
Most lung cancer statistics include both small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC). In general, about 10% to 15% of all lung cancers are SCLC, and about 80% to 85% are NSCLC.
Lung cancer (both small cell and non-small cell) is the second most common cancer in both men and women in the United States (not counting skin cancer). In men, prostate cancer is more common, while breast cancer is more common in women.
The American Cancer Society’s estimates for lung cancer in the US for 2024 are:
About 234,580 new cases of lung cancer (116,310 in men and 118,270 in women)
About 125,070 deaths from lung cancer (65,790 in men and 59,280 in women)
Lung Cancer Statistics How Common is Lung Cancer? American Cancer Society
Worldwide, an estimated 2,206,771 people were diagnosed with lung cancer in 2020. These statistics include both small cell lung cancer and NSCLC.
Lung Cancer - Non-Small Cell: Statistics Cancer.Net
~Author Calculations/Estimates~
Approximately 187,664 cases of NSCLC in the US based on an 80% factor.
Approximately 1,765,416 cases of NSCLC worldwide based on an 80% factor.
~Prevalence of Thyroid Cancer~
Rate of New Cases and Deaths per 100,000: The rate of new cases of thyroid cancer was 13.5 per 100,000 men and women per year. The death rate was 0.5 per 100,000 men and women per year. These rates are age-adjusted and based on 2017–2021 cases and 2018–2022 deaths.
Lifetime Risk of Developing Cancer: Approximately 1.2 percent of men and women will be diagnosed with thyroid cancer at some point during their lifetime, based on 2017–2019 data. Lifetime risk based on data through 2022 will available soon.
Prevalence of This Cancer: In 2021, there were an estimated 979,295 people living with thyroid cancer in the United States.
Thyroid Cancer — Cancer Stat Facts
About 44,020 new cases of thyroid cancer (12,500 in men and 31,520 in women)
About 2,170 deaths from thyroid cancer (990 in men and 1,180 in women)
Thyroid cancer is often diagnosed at a younger age than most other adult cancers. The average age when a person is diagnosed with thyroid cancer is 51.
This cancer is about 3 times more common in women than in men. It is about 40% to 50% less common in Black people than in any other racial or ethnic group.
Key Statistics for Thyroid Cancer American Cancer Society)
Addressable Market
Given Gavreto’s dual treatment capacity, the total amount of potential patients with NSCLC with RET+ indications would be approximately 2,800 cases in the US and approximately 26,500 cases worldwide each year using a factor of 1.5% of total NSCLC cases. The total amount of treatable cases for Thyroid Cancer would be approximately 650 in the US and 16,500 cases worldwide respectively each year applying the same 1.5% RET+ percentage rate. DOUBLE CHECK MATH…
~Rigel Pharmaceuticals Pipeline~
~IRAK/4 – Clinical Trials~
Rigel’s investigational candidate, R289, is an oral, potent and selective inhibitor of interleukin receptor-associated kinases 1 and 4 (IRAK1/4).
Toll like receptors (TLRs) and the interleukin 1 receptor family (IL-1Rs) play a critical role in the innate immune response and dysregulation of these pathways can lead to a variety of inflammatory conditions such as psoriasis, rheumatoid arthritis, and inflammatory bowel disease. Chronic stimulation of both receptor systems has also been implicated in causing a pro-inflammatory bone marrow environment leading to persistent cytopenias in lower-risk myelodysplastic syndrome (LR-MDS) patients1.
R835 is a selective dual inhibitor of IRAK1/4 that blocks TLR4 and IL-1R-dependent systemic cytokine release. In preclinical studies, R835 demonstrated activity in multiple animal models of inflammatory disease2,3 and showed that dual inhibition of IRAK1 and IRAK4 provided more complete suppression of inflammatory cytokines when compared to an IRAK4-selective inhibitor4.
Development of R289:
In a Phase 1 clinical trial, R835 was well tolerated and inhibited LPS-induced inflammatory cytokine production in healthy volunteers, demonstrating proof-of-mechanism.5 Phase 1 clinical studies of R289 (an oral prodrug that is rapidly converted to R835 in the gut) are also complete.
A Phase 1b open-label, multicenter trial of R289 in patients with relapsed/refractory lower-risk MDS is currently enrolling (NCT05308264). The primary endpoint for this trial is safety with key secondary endpoints including preliminary efficacy and evaluation of pharmacokinetic properties.
~Bemcentinib – Bergenbio Partnership~
In June 2011, Rigel entered into an exclusive, worldwide research, development and commercialization agreement with BerGenBio for its investigational AXL receptor tyrosine kinase (AXL) inhibitor, R428 (now referred to as bemcentinib).
Bemcentinib is a potent, selective and orally bioavailable AXL inhibitor and the furthest along in clinical trials. In preclinical studies, bemcentinib was shown to have an effect as a single agent therapeutic in the prevention and reversal of acquired resistance to standard of care cytotoxics and targeted therapies and may also slow or prevent tumor metastasis.
Rigel received an upfront payment and is eligible for milestone payments and potential sublicensing revenue, as well as tiered royalty payments on any future net sales of products emerging from the collaboration.
~R552 Systemic – Eli Lilly Partnership~
Rigel’s investigational candidates are oral, potent and selective inhibitors of receptor-interacting serine/threonine-protein kinase 1 (RIPK1).
RIPK1 is a critical signaling protein implicated in a broad range of key inflammatory cellular processes including necroptosis, a type of regulated cell death, and cytokine production. In necroptosis, cells rupture leading to the dispersion of cell contents, which can trigger an immune response and enhance inflammation. RIPK1 inhibition has therapeutic potential in treating autoimmune, inflammatory, and neurodegenerative disorders.
Rigel’s RIPK1 inhibitor program includes R552, a systemic molecule being developed for the treatment of autoimmune and inflammatory disorders, and brain penetrating RIPK1 inhibitors for central nervous system (CNS) diseases. In preclinical studies, R552 demonstrated prevention of joint and skin inflammation in a RIPK1-mediated murine model of inflammation and tissue damage.
Development of R552:
In Q2 2023, the initial Phase 2a trial (NCT05848258) in moderately to severely active rheumatoid arthritis (RA) was initiated by partner Eli Lilly.
Development CNS-penetrating RIPK1 inhibitors:
Currently in preclinical studies.
~Milademetan – Daiichi Sankyo Partnership~
Rigel has a long-standing collaboration with Daiichi-Sankyo for developing murine double minute 2 (MDM2) protein inhibitors in cancer, which were discovered in Rigel’s laboratories.
Preliminary safety and efficacy data from an early Phase 1 study of milademetan (formerly DS-3032), an oral selective MDM2 inhibitor, in hematological malignancies suggests that it may be a promising potential treatment for oncology indications.
Rigel received an upfront payment and is eligible for milestone payments, as well as tiered royalty payments on any future net sales of any products emerging from the collaboration.
~Rxxx (CNS Penetrant) – Eli Lilly Partnership~
Rigel’s investigational candidates are oral, potent and selective inhibitors of receptor-interacting serine/threonine-protein kinase 1 (RIPK1).
RIPK1 is a critical signaling protein implicated in a broad range of key inflammatory cellular processes including necroptosis, a type of regulated cell death, and cytokine production. In necroptosis, cells rupture leading to the dispersion of cell contents, which can trigger an immune response and enhance inflammation. RIPK1 inhibition has therapeutic potential in treating autoimmune, inflammatory, and neurodegenerative disorders.
Rigel’s RIPK1 inhibitor program includes R552, a systemic molecule being developed for the treatment of autoimmune and inflammatory disorders, and brain penetrating RIPK1 inhibitors for central nervous system (CNS) diseases. In preclinical studies, R552 demonstrated prevention of joint and skin inflammation in a RIPK1-mediated murine model of inflammation and tissue damage.
Development of R552:
In Q2 2023, the initial Phase 2a trial (NCT05848258) in moderately to severely active rheumatoid arthritis (RA) was initiated by partner Eli Lilly.
Development CNS-penetrating RIPK1 inhibitors:
Currently in preclinical studies. Pipeline :: Rigel Pharmaceuticals, Inc. (RIGL)
~Summary and Prediction~
The current share price of sub $1 does not feel justified. I would anticipate financial breakeven by the end of 2024 or potentially in Q1 or Q2 of 2025. The robust pipeline, progress, and expected revenue growth are enough to justify a much higher valuation. The debt load is manageable, but the potential for S is concerning. I believe that the S is not necessary and revenue growth and progress should speak for itself. I am not as bullish as the analysts at HC Wainright for a $15 PT, but the valuation should be at least 3x to 5x from the current value. This thesis does not highlight the patents surrounding their drugs either which some extend into 2035 and beyond. Perhaps what Wall Street is discounting is the fact that most of the drugs are very niche. However, the currently available drugs have an addressable market, albeit less universal than some, but you should value it in the sense of multiple facets (a 1000 headed snake is the phrase I wanted to use). I believe the company should be valued with specialty drugs in mind which would command a higher PE ratio. At the current day and time of writing, the value should be at least $1.50 to $1.75 ~at a minimum~ with a 12 month price target of $3 to $5+. I will be looking for continued revenue growth in each quarter this year and realization of revenue from Gavreto in Q2 or Q3 this year. The partnerships should not be discounted either and the current share price if it lingers here perhaps may attract a merger or acquisition. I initially began the research thinking that perhaps the drugs were too niche, but given the multiple drugs they are working with, I believe their revenue sources will continue to grow if you do not focus on one particular drug as the main performer. With the most recent inflation report being cooler than expected, I would suspect larger funds and institutions will be circling back to riskier assets.

HOWDY Partners 🤠 I type this important message from the southern region of the United States. If your lookin for someone who will respond back to your messages in 1.2 milliseconds, well look no further. My interest include and are not limited too (if our hobbies are different please tell me about yours I’m always looking for new ones for my ADHD brain): •Gaming, of course who doesn’t game in this day in age. •Watching 10 movies in a row and not feeling bad about it. •Blasting music at night daydreaming scenarios in my head staring at the blank void filled walls. I have a ton more but I’d figured I’d save them for the meat of our chat. Hope to hear from whatever soul is reading this post. Peace and Love ✌️&❤️

I need opinions. I’ve been a nurse for 13 years, mainly ICU and PACU. After major burnout tried GI clinic, couldn’t do the sitting at a desk five days a week. Now I’m doing home health. Really liked it at first, liked moving around all day and meeting different patients, doing some actual hands-on care again. I signed on for 32 hour week so I could catch a break even though it’s a bit of a pay cut.
Fast forward to three months in. They took me off orientation like 4-5 weeks early due to two of the other RNs going on LOA (classic). They told me they’d give me a company car and no one’s answering me when I inquire about it (have tried twice now). I was told 1 weekday and 1 weekend on-call shift per month when I interviewed. I was put on call for the first time Mon/tues/wed this week (4p-8a the next day between my shifts) and am now on-call Sat and Sun (8am Sat-8am Mon). They’ve assigned me an admission visit each day (like 2 hour visit plus 2 hrs of documentation), two check in calls and a follow up visit. Then Monday I have a full patient load and start my new week. To me that’s not on-call, that’s weekend shifts.
Like wtf? So I’ll only have one day off in two weeks essentially. Not to mention, I signed up for 32 hours and have been working btwn 40-50.
Home health RNs, does this sound typical? Cause from everything I’ve heard most people love this job but this SUCKS.
Thanks in advance, RN in career crisis

I'm embarrassed to post this, sorry forbthe picture, I wanted to see if there's anyone who can relate to what I'm going through.
Symptoms one month ago • full after eating 3 bites • very nauseous before and after eating • no appetite • dizzy and off balance • legs swelling • mid back pain • diarrhea/light color stool/yellow-Red mucus/floating stool
Symptoms previously • legs swelling • shortness of breath-while holding 5 or more pounds • fast heartbeat when moving • bowel movement 2 to 3 days • dizzy off balance • stool yellow on paper
Background, my TSH was at a 2.6 in January, go my levels checked this week TSH is at a 4.5, it never goes up that much in a short period of time, I was feeling fine intel I took 50,000 vitamin D for 8 weeks(1 pill a week) on the 3rd week I was • had more energy • loss 5 pounds • nothing pointed to my thyroid
Than 2 more weeks into taking vitamin D • bones are aching/body pains • limping/numbness in both legs+swelling • stool this yellow on paper • constipation ect • lots of belching=tasting food from the night before/lot of foul smelling gas This has been going on for 3 months now
I have a doctor appointment with my endocrinologist on Monday and a G.I appointment on July 31st, I really hope the G.I doc doesn't dismiss my symptoms Because of my thyroid, I've had this same symptoms come and go for 4 years. Thank you for reading my long post