personal_noteS – Page 19

CAR-T Therapies: 2+ Years Into Commercialization (1)

Approvals and Acquisition

Back in 2017, when Kymriah by Novartis was first approved by FDA, it marked the beginning of commercializing CAR-T cell therapies in the US.

CAR-T therapies have shown superior effects in treating blood cancers. Kymriah’s initial approved indication is B-cell precursor ALL that is refractory or in second or later relapse for patients up to 25 years of age. There are approximately 3,100 patients aged 20 and younger are diagnosed with ALL each year; 15-20 percent of pediatric B cell precursor ALL patients relapse after their initial remission.

On Aug 28, 11 days after Kymriah’s approval, another CAR-T cell therapy company Kite Pharma was acquired by Gilead for $11.9 billion. The $180.00 per share acquisition price represents a 29% premium to Kite’s closing on Friday, August 25, and a 50% premium to the company’s 30-day volume weighted average stock price.

At the time of acquisition, Kite’s lead candidate was under FDA’s priority review and had submitted the first CAR-T therapy application in Europe for the treatment of relapsed/refractory DLBCL, TFL and PMBCL with the European Medicines Agency (EMA).

On Oct 18, FDA approved Kite’s Yescarta for use in adult patients with large B-cell lymphoma after at least two other kinds of treatment failed, including diffuse large B-cell lymphoma (DLBCL), primary mediastinal large B-cell lymphoma, high grade B-cell lymphoma and DLBCL arising from follicular lymphoma. DLBCL is the most common type of NHL in adults, with 24,000 new cases diagnosed each year in the US (1/3 of newly diagnosed NHL).

Concurrently, in Gilead’s press release, it estimated that in the US each year there are approximately 7,500 patients with refractory DLBCL who are eligible for CAR T therapy.

In May 2018, FDA expanded Kymriah’s approval for adults with relapsed or refractory large B-cell lymphoma as well.

In August 2018, Yescarta received European Marketing Authorization for adult patients with relapsed or refractory DLBCL and PMBCL, after two or more lines of systemic therapy; Kymriah was approved in EU for the treatment of pediatric and young adult patients up to 25 years of age with B-cell acute lymphoblastic leukemia (ALL) that is refractory, in relapse post-transplant or in second or later relapse; and for the treatment of adult patients with relapsed or refractory (r/r) diffuse large B-cell lymphoma (DLBCL) after two or more lines of systemic therapy.

In March 2019, Japan’s Ministry of Health, Labor and Welfare (MHLW) has approved Kymriah (tisagenlecleucel) for the treatment of two distinct indications – CD19-positive relapsed or refractory (r/r) B-cell acute lymphoblastic leukemia (ALL) and CD19-positive r/r diffuse large B-cell lymphoma (DLBCL).

Clinical Trails and Data

r/r ALL

Kymriah was first approved by FDA based on 82.5% overall remission rate (ORR) reported at 3 months, of which all were MRD– (n=52/63).

lower limit of the 95% confidence interval for ORR is 70.9%, which is above the pre-set null hypothesis rate of 20%
40 subjects (63.5%) had the best response of CR within the first 3 months after infusion
12 subjects (19.0%) had the best response of CRi.
Among the 52 responders, the median duration of response (DOR) was not yet reached (range: 1.2 to 14.1+ months) with the median follow-up of 4.8 months.
84% (n=57) experienced Grade 3 or higher events
Cytokine release syndrome (CRS) occurred in 79% of patients; CRS Grade 3 or higher occurred in 49% of patients

On ASH 2018, Novartis presented an updated ORR rate of 82.3% (n=65/79); relapse-free survival was 62% at 24 months.

ORR and MRD Remission

r/r DLBCL

Yescarta was approved in 2017 based on an ORR of 72% (n=73/101), with a CR rate of 51%. SAEs Grade 3 or higher occurred in 48 (44%) patients. CRS occurred in 94% of patients; CRS Grade 3 or higher occurred in 13% of patients.

On ASH 2019, Gilead provided updates on ZUMA-1 that median overall survival (OS) was 25.8 months.

When Kymriah was approved for r/r DLBCL in 2018, the overall response rate (ORR) was 50% at 3 months (n=34/68). On ASH 2019, in the 24-month analysis of the JULIET trial, ORR was 52% (N=115).

Suntory And Whisky (2)

Current Availability

Suntory’s whiskies, especially Yamazaki, has been in shortage in the past few years; the prices have been increasing constantly.

This week, Suntory unveiled a limited edition 55-year-old Yamazaki single malt whisky, which it will sell for 3 million yen ($27,347.31) a bottle. Only 100 bottles will be sold from June 30, and buyers will be chosen by lottery. Blended from whisky matured in mizunara and white oak casks, the edition will be the oldest version of Yamazaki.

The company in 2005 sold a limited edition of a 50-year-old Yamazaki for 1 million yen. One of them auctioned by Bonhams in Hong Kong in 2018 fetched HK$2.695 million.

In May 2018, it was reported that sales of Hakushu 12 Year and Hibiki 17 Year to be suspended in Jun 2018. Suntory said the demand was far outstripping supply and distillers were not being able to produce enough of it.

Before that, the demand for the Hibiki 12 year has become unsustainable and in 2015 Suntory announced it would be discontinuing the expression.

Currently the most commonly seen versions for Yamazaki are 12yr, 18yr, 30yr and Distiller’s Reserve (no age).

The Distiller’s Reserve version was launched in 2014, containing a range of liquid aged from around eight to 20 years. Blended by Suntory chief blender Shinji Fukuyo, the Yamazaki Distiller’s Reserve is a vatting of whisky matured in French oak Bordeaux wine casks, Sherry casks, mizunara casks (Japanese oak) and American oak casks, with some peated malt added. [thespiritsbusiness]

Awards (Whisky Bible: WORLD WHISKIES OF THE YEAR)

2016: Suntory Yamazaki Mizunara (Bot.2014) (ranked 5th our of 5 picks)
2015: The Yamazaki Single Malt Sherry 2013 (ranked 1st out of 3 picks)

Awards (World Whiskies Awards)

2019 WORLD’S BEST BLENDED WHISKY – Hibiki 21 Years Old
2018 WORLD’S BEST SINGLE MALT – Hakushu 25 Years Old
2017 WORLD’S BEST BLENDED – Hibiki 21 Years Old
2016 WORLD’S BEST BLENDED – Hibiki 21 Years Old

Awards (International Spirits Challenge, Gold)

Yamazaki

2007 – The YAMAZAKI Single Malt Whisky 18 years old
2009 – Yamazaki 1984
2010 – The YAMAZAKI single malt whisky 12YO
2010 – The YAMAZAKI single malt whisky 18YO
2011 – The Yamazaki Single Malt Whisky 1984
2012 – The Yamazaki Single Malt Whisky Aged 18 Years
2013 – The Yamazaki single malt whisky Puncheon 2012
2013 – The Yamazaki single malt whisky Mizunara 2012
2013 – The Yamazaki single malt whisky 18 Years Old
2014 – THE YAMAZAKI SINGLE MALT WHISKY MIZUNARA 2013
2014 – THE YAMAZAKI SINGLE MALT WHISKY BOURBON BARREL 2013
2014 – THE YAMAZAKI SINGLE MALT WHISKY 18 YEARS OLD
2015 – THE YAMAZAKI SINGLE MALT WHISKY MIZUNARA 2014
2017 – The Yamazaki Single Malt Whisky Limited Edition 2016
2018 – THE YAMAZAKI SINGLE MALT WHISKY 12 YEARS OLD
2018 – THE YAMAZAKI SINGLE MALT WHISKY 18 YEARS OLD
2019 – THE YAMAZAKI SINGLE MALT WHISKY MIZUNARA 2017 EDITION

Hakushu

2008 – Single Malt Whisky “Hakushu” aged 25 years
2009 – Hakushu 18 y.o.
2010 – The HAKUSHU single malt whisky 25YO
2010 -The HAKUSHU single malt whisky HEAVILY PEATED
2011 – The Hakushu Single Malt Whisky Bourbon Barrel
2012 – The Hakushu Single Malt Whisky Aged 25 Years
2012 -The Hakushu Single Malt Whisky Aged 12 Years
2012 – The Hakushu Single Malt Whisky Sherry Cask (12 years old and under)
2013 – The Hakushu single malt whisky Heavily Peated 2012
2013 – The Hakushu single malt whisky 25 Years Old
2013 – The Hakushu single malt whisky 18 Years Old
2014 – THE HAKUSHU SINGLE MALT WHISKY SHERRY CASK 2014
2014 – THE HAKUSHU SINGLE MALT WHISKY 25 YEARS OLD
2014 – THE HAKUSHU SINGLE MALT WHISKY 18 YEARS OLD
2015 – THE HAKUSHU SINGLE MALT WHISKY 25 YEARS OLD
2016 – The Hakushu Single Malt Whisky 25 Years Old
2016 – The Hakushu Single Malt Whisky 18 Years Old
2017 – The Hakushu Single Malt Whisky 25 Years Old
2017 – The Hakushu Single Malt Whisky 18 Years Old
2019 – THE HAKUSHU SINGLE MALT WHISKY 25 YEARS OLD
2019 – THE HAKUSHU SINGLE MALT WHISKY 18 YEARS OLD

Hibiki

2009 – Hibiki 17 y.o.
2010 – SUNTORY Whisky HIBIKI 12YO
2010 – SUNTORY Whisky HIBIKI 21YO
2012 – Hibiki Japanese Blended Whisky Aged 21 Years
2012 – Hibiki Japanese Blended Whisky Aged 17 Years
2013 – Hibiki Japanese Blended Whisky aged 17 years
2013 – Hibiki Japanese Blended Whisky aged 12 years
2014 – HIBIKI JAPANESE BLENDED WHISKY DEEP HARMONY
2014 – HIBIKI JAPANESE BLENDED MELLOW HARMONY
2015 – HIBIKI JAPANESE BLENDED WHISKY AGED 12 YEARS
2016 – Suntory Whisky Hibiki 17 Years Old
2016 – Suntory Whisky Hibiki Mellow Harmony
2017 – Suntory Whisky Hibiki Japanese Harmony Master’s Select
2019 – SUNTORY WHISKY HIBIKI JAPANESE HARMONY Master’s Select

Chita

2017 – Suntory Single Grain Whisky Chita Distillery

Suntory And Whisky (1)

A History of Suntory’s Three Whisky Distilleries

The founder of Suntory, Shinjirō Torii (born in 1879), started with selling imported wine in Osaka in 1899.

Incorporation – the store became the Kotobukiya company in 1921.

In 1923, the Yamazaki Distillery was constructed – Japan’s first malt whisky distillery. It was built in the town called Yamazaki 山崎町 (now in Shisō 宍粟市, Hyōgo 兵库县), on the periphery of Kyoto. This region was formerly referred to as “Minaseno”, where one of the purest waters of Japan originates. Yamazaki Distillery is where the Katsura, Uji and Kizu rivers converge, providing a unique misty climate and one of Japan’s softest waters. The diversity of this region’s temperature and humidity creates ideal conditions for cask aging, known as the signature “Suntory Maturation”.

Production began in 1924 and five years later it launched Japan’s first single-malt whisky Suntory Whisky Shirofuda (white label) in 1929.

Keizo Saji (Torii’s son) becomes 2nd president in 1961 (at age of 42); Shinjirō Torii passed away in 1962.

In 1963, Kotobukiya changed its name to “Suntory” from “Torysan”, taken from the name of the whisky it produces.

In the same year, Musashino Beer Factory (in Fuchū 府中市, Tokyo 东京都) began its production of the Suntory Beer.

In 1972, Keizo built Chita Distillery on the shores of Chita Peninsula (Chita 知多市, Aichi 爱知县).

In 1973, Hakushu Distillery was established, in the Toribara locality of the former town of Hakushū 白州町 (now part of Hokuto 北杜市 in Yamanashi 山梨县), It is located in the foothills of Mt. Kaikomagatake.

1980s – Distilleries Becoming Brands

Until the 1980s, whisky made at Yamazaki was bottled as Suntory blends. It began to market their distilleries in the way the Scottish market theirs, by branding the whisky for the distillery at which it is made. [Japanese Whisky Handbook by Gary Clark]

Saji pioneered the distillery’s move into single malt whisky in 1984, with the launch of Suntory Single Malt Whisky Yamazaki – the first time Yamazaki is used as the brand name. This was followed by Yamazaki 18 Years Old in 1992. [thespiritsbusiness]

In 1989, the 90th anniversary of the company’s founding, Suntory Hibiki was released. It is a blended whisky using whiskies from the three distilleries Yamazaki, Hakushu, and Chita.

Shinichiro Torii becomes the 3rd president in 1990.

In 1994, Hakushu Single Malt Whisky is launched.

In 2003, the Yamazaki 12 Years single malt whisky became the first Japanese whisky to win the gold medal at the International Spirits Challenge, the most authoritative liquor competition in the world.

Online Higher Education (6): 2U’s Graduate Programs

Charting for 2U : 1) insignificant growth for fee-for-degree programs since 2019; 2) more diversified with expensive fee-for-certificate programs.

Online Higher Education (5) – Education Company Stocks

A Python Generated Graph On Airlines’ Load Factors

Major airlines usually would post their monthly operation results on IR websites. While United Airlines and Southwest Airlines among other stopped reporting in 2019, Alaska and Delta are still doing so.

Load factor is a measure of the use of aircraft capacity that compares Revenue Passenger-Miles as a proportion of Available Seat-Miles.

Below is a three-part project that automatically downloads, summarizes and creates chart for 4 airlines’ load factor.

Download

Given certain years, the program will go through pre-defined links to search for monthly report urls and scrap relevant data based on the page structure. BeautifulSoup is used here.

Summary

The program uses file reading and writing to put four airlines’ data together while adjusting for missing data (aligning based on month)

Charting

The program converts csv to excel and draws the chart based on data. pandas and xlsxwriter are used here.

With some adjustments, the program should be able to scrape and virtualize other web-based standard reports.

China Drugstores: # Of Stores, Drugstore Chains, Share Of Top 10 Chains

The independent drugstores will find it harder to compete and the percentage of drugstore chain’s locations will steadily increase.

The “50% chain rate by 2020” target was set in 2016. In US and Japan, the percentage of chain stores is over 70%.

Source: www.sfdaic.org.cn/statistics

The market share in sales for top chains keeps increasing, as their sales grow faster than industry average.

Source: 中国药店，中信证券

* the total drug retail sales data is a little different from the previous post China Medicine End Market Sales (2018: 391.9 vs. 400.2 billion RMB, 2% higher in this report)

China Medicine End Market Sales Data

Data estimated by 米内网 (menet.com), which was formerly 中国医药经济信息网, created in 1997 by (formerly) CFDA Southern Research Institute.

According to the data, the overall end market sales grew 6.3% to 1713 billion yuan (or ~$250 billion) in 2018.

Retailer channels continues to grew at above-GDP rate (7.5% in 2018).

The data is not including sales in private hospitals/clinics, etc. The overall sales would be 2 trillion yuan for 2018 if included.

Online Higher Education (2) – MOOCs

Developed from universities

The history of massive open online course (MOOC) dated back to 2008 (by Stephen Downes and George Siemens entitled Connectivism and Connectivity Knowledge). The intention was to exploit the possibility for interactions between a wide variety of participants made possible by online tools so as to provide a richer learning environment than traditional tools would allow.

MOOCs with an emphasis on interactions and connectivity are now called cMOOCS.

In the fall of 2011, Stanford offered three courses for free online. Peter Norvig and Sebastien Thrun offered their Introduction to Artificial Intelligence to an initial enrollment of over 160,000 students from around the world. Over 20,000 students completed the course. These xMOOCs focused less on interaction between students and more on exploiting the possibilities of reaching a massive audience.

Nowadays, through MOOCs, anyone with internet access can take some of the most famous courses taught by world-class professors for free, such as Harvard’s Justice. And courses on updated topics such as The Opioid Crisis in America by Harvard Medical School.

Transformed to independent organizations…

Seeing their success of MOOCs, Thrun founded a company called Udacity in February 2012 which began to develop and offer MOOCs for free. Udacity is funded by venture capital firm, Charles River Ventures, and $200,000 of Thrun’s personal money. In October 2012, the venture capital firm Andreessen Horowitz led the investment of another $15 million in Udacity.

Andrew Ng and Daphne Koller, two other Stanford CS professors started Coursera in April 2012 with three classes in fall 2011 from Stanford.

We will come back to these companies later. But let’s first take a look at a non-profit effort – edX.

edX

The establishment of edX was traced back to MIT’s effort – MITx platform. Announced in Dec 2011, MITx platform is led by Prof Anant Agarwal to offer MOOCs as a constituent program of MIT’s Office of Digital Learning.

Harvard joined forces with MIT in May 2012 when the two schools pooled $60 million in resources and renamed/spun-off the open platform component into edX, a non-profit organization. Open edX is the massively scalable learning software platform behind edX.

Since the origin of MOOCs, which are basically free for users, monetization methods are explored to make those platforms sustainable.

In Sep 2012, edX, partnering with Pearson, introduced “proctored exams” option, which would charge a small fee. edX learners have the option of taking a course final exam at one of over 450 Pearson VUE test centers.

Full fee-for-certificates models were introduced in 2013 following the industry trend.

Students can pay a fee to receive an ID-verified certificate upon successful completion of class requirements. Debuting in Fall 2013, three initial paid certificates would cost $25 for Stat2x: “Introduction to Statistics,” $50 for CS169x: “Software as a Service,” and $100 for 6x: “Circuits and Electronics.”

edX launched grouped-courses-based programs (XSeries) in Sep 2013, and MicroMasters programs in 2016, which may count as credits towards master degrees.

XSeries usually costs several hundred dollars with certificates and includes 3-5 courses. If taken separately, those courses usually can be access for free without certificates.

For MicroMasters, they are more linked with institutions and existing degrees.

As an example, the MicroMasters® Program in Supply Chain Management, can be used to apply to MIT’s SCM program which awards the Master of Engineering in Logistics (M.Eng. Logistics). The degree will also require another semester of on-campus study. The MicroMasters Program in SCM is also accepted in other universities worldwide.

The MicroMasters in SCM has five online courses. The cost to take each course is US$200. The cost to sit for the Comprehensive Final Exam is $200. The overall cost of the five course plus the final exam is US$1200. And the package can be purchased through edX with a 10% discount.

To be continued

Online Higher Education (1)

US Higher Education

According to The Condition of Education 2019 by National Center for Education Statistics (NCES):

Undergraduate Enrollment
- In fall 2017, total undergraduate enrollment in degree-granting postsecondary institutions was 16.76 million students.
- Between 2000 and 2017, total undergraduate enrollment in degree-granting postsecondary institutions increased by 27 percent (from 13.2 million to 16.8 million students).
- By 2028, total undergraduate enrollment is projected to increase to 17.2 million students.
- Percentage enrolled in any distance education course grew from 30.8% to 32.9% ▲
- Percentage enrolled exclusively in distance education grew from 12.8% to 13.3% ▲
Post-baccalaureate Enrollment
- In fall 2017, some 3.0 million students were enrolled in post-baccalaureate degree programs.
- Between 2000 and 2017, total post-baccalaureate enrollment increased by 39 percent (from 2.2 million to 3.0 million students).
- By 2028, post-baccalaureate enrollment is projected to increase to 3.1 million students.
- Percentage enrolled in any distance education course grew from 32% to 34% ▲
- Percentage enrolled exclusively in distance education grew from 15% to 16% ▲

NCES is located within the U.S. Department of Education and the Institute of Education Sciences. Distance education is a broad definition here but is an approximate to online education.

We can see that:

Online education is one of the fastest growing forms of higher education.
Around 1/3 of those enrollments have used online courses.
Online degree programs have grown at least to 13-16% – as many programs will require on-campus immersions to some extent.

Another report by Wiley Education Services said by the 2020/21 school year, online programs are expected to account for 26% of all higher education market share.

It also lays out some headwinds & tailwinds.

To be continued